Role Of Microtubules Research Articles

Molecular basis for the assembly of the dynein transport machinery on microtubules.

Cytoplasmic dynein-1, a microtubule-based motor protein, requires dynactin and an adaptor to form the processive dynein-dynactin-adaptor (DDA) complex. The role of microtubules in DDA assembly has been elusive. Here, we reveal detailed structural insights into microtubule-mediated DDA assembly using cryo-electron microscopy. We find that an adaptor-independent dynein-dynactin complex (DD) predominantly forms on microtubules in an intrinsic 2:1 stoichiometry, induced by spontaneous parallelization of dynein upon microtubule binding. Adaptors can squeeze in and exchange within the assembled microtubule-bound DD complex, which is enabled by relative rotations between dynein and dynactin, and further facilitated by dynein light intermediate chains that assist in an adaptor 'search' mechanism. Our findings elucidate the dynamic adaptability of the dynein transport machinery, and reveal a new mode for assembly of the motile complex.

Hydroxyethylamine based analog targets microtubule assembly: an in silico study for anti-cancerous drug development

Microtubules are dynamic cytoskeletal structures essential for cell architecture, cellular transport, cell motility, and cell division. Due to their dynamic nature, known as dynamic instability, microtubules can spontaneously switch between phases of growth and shortening. Disruptions in microtubule functions have been implicated in several diseases, including cancer, neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, and birth defects. The role of microtubules during various phases of the cell cycle, particularly in cell division, makes them attractive targets for drug development against cancer. Several successful drugs currently on the market are designed to target microtubules. However, the presence of cellular toxicity and the development of multidrug resistance necessitate the search for new microtubule-targeting drugs.Here, a library of 106 biologically active compounds were screened to identify potent microtubule assembly inhibitors. Out of all the screened compounds, the hydroxyethylamine (HEA) analogues are found to be the best hit.We identified three inhibitors, BKS3031A, BKS3045A and BKS3046A, that bind at the same site as the well-known microtubule targeting agent colchicine. These inhibitors were simulated for 100 ns with tubulin complexes, and the results indicated that they remain stable within the binding pocket of α-β tubulin complexes. In addition, we estimated the binding free energy of BKS3031A, BKS3045A and BKS3046A by using molecular mechanics generalized Born surface area (MM-GBSA) calculations, and it was found to be -32.67 ± 6.01, -21.77 ± 5.12 and − 22.92 ± 5.09 kcal/mol, respectively. Our findings suggest that these novel inhibitors have potential to bind and perturb the microtubule network, positioning them as promising microtubule-targeting agents.

Quantum consciousness: A synthesis of SOC and Orch-OR

Despite the advances in the neuroscience field, the nature of consciousness and the mind-body problem are still unsolved. No conventional neurophysiological method has been able to explain consciousness, other than focusing on neural signals. Various theories, such as Orchestrated Objective Reduction (Orch-OR), Higher Order Theory, Global Workspace Theory, and Integrated Information Theory, also have serious limitations. To better understand the nature of consciousness, the present work explores the connection between Quantum Mechanics and Statistical Physics, in particular through the Orch-OR theory and Self-Organized Criticality (SOC). SOC provides an explanation of how complex systems naturally tend toward critical states, whereas Orch-OR posits that consciousness arises from quantum computations in neuronal microtubules. Here, an integration of these hypotheses is pit forward, proposing that microtubules function as quasi-critical systems that undergo second-order phase transitions, thus generating objective reduction and, consequently, a conscious experience. This idea provides a theoretical framework for the interpretation of how microtubules may contribute to the orchestration of consciousness by integrating quantum coherence and criticality. Future research will be directed toward the biochemical constituents that maintain the essential aspects of microtubule quantum states, their connection to cognitive functions, and experimental verification of these states. This synthesis provides a novel perspective on the role of microtubules in the brain and the quantum foundations of consciousness.

CAMSAP3 forms dimers via its α-helix domain that directly stabilize non-centrosomal microtubule minus ends.

Microtubules are vital components of the cytoskeleton. Their plus ends are dynamic and respond to changes in cell morphology, while the minus ends are stable and serve a crucial role in microtubule seeding and maintaining spatial organization. In mammalian cells, the calmodulin-regulated spectrin-associated proteins (CAMSAPs), play a key role in directly regulating the dynamics of non-centrosomal microtubules minus ends. However, the molecular mechanisms are not yet fully understood. Our study reveals that CAMSAP3 forms dimers through its C-terminal α-helix; this dimerization not only enhances the microtubule-binding affinity of the CKK domain but also enables the CKK domain to regulate the dynamics of microtubules. Furthermore, CAMSAP3 also specializes in decorating at the minus end of microtubules through the combined action of the microtubule-binding domain (MBD) and the C-terminal α-helix, thereby achieving dynamic regulation of the minus ends of microtubules. These findings are crucial for advancing our understanding and treatment of diseases associated with non-centrosomal microtubules.

Microtubules Disruption Alters the Cellular Structures and Mechanics Depending on Underlying Chemical Cues.

The extracellular matrix determines cell morphology and stiffness by manipulating the cytoskeleton. The impacts of extracellular matrix cues, including the mechanical and topographical cues on microtubules and their role in biological behaviors, are previously studied. However, there is a lack of understanding about how microtubules (MTs)are affected by environmental chemical cues, such as extracellular matrix density. Specifically, it is crucial to understand the connection between cellular morphology and mechanics induced by chemical cues and the role of microtubules in these cellular responses. To address this, surfaces with high and low cRGD (cyclic Arginine-Glycine-Aspartic acid) peptide ligand densities are used. The cRGD is diluted with a bioinert ligand to prevent surface native cellular remodeling. The cellular morphology, actin, and microtubules differ on these surfaces. Confocal fluorescence microscopes and atomic force microscopy (AFM) are used to determine the structural and mechanical cellular responses with and without microtubules. Microtubules are vital as an intracellular scaffold in elongated morphology correlated with low cRGD compared to rounded morphology in high cRGD substrates. The contributions of MTs to nucleus morphology and cellular mechanics are based on the underlying cRGD densities. Finally, this study reveals a significant correlation between MTs, actin networks, and vimentin in response to the underlying densities of cRGD.

RREB1 regulates neuronal proteostasis and the microtubule network.

Transcription factors play vital roles in neuron development; however, little is known about the role of these proteins in maintaining neuronal homeostasis. Here, we show that the transcription factor RREB1 (Ras-responsive element-binding protein 1) is essential for neuron survival in the mammalian brain. A spontaneous mouse mutation causing loss of a nervous system-enriched Rreb1 transcript is associated with progressive loss of cerebellar Purkinje cells and ataxia. Analysis of chromatin immunoprecipitation and sequencing, along with RNA sequencing data revealed dysregulation of RREB1 targets associated with the microtubule cytoskeleton. In agreement with the known role of microtubules in dendritic development, dendritic complexity was disrupted in Rreb1-deficient neurons. Analysis of sequencing data also suggested that RREB1 plays a role in the endomembrane system. Mutant Purkinje cells had fewer numbers of autophagosomes and lysosomes and contained P62- and ubiquitin-positive inclusions. Together, these studies demonstrate that RREB1 functions to maintain the microtubule network and proteostasis in mammalian neurons.

Microtubule-Mediated Regulation of β2AR Translation and Function in Failing Hearts.

β1AR (beta-1 adrenergic receptor) and β2AR (beta-2 adrenergic receptor)-mediated cyclic adenosine monophosphate signaling has distinct effects on cardiac function and heart failure progression. However, the mechanism regulating spatial localization and functional compartmentation of cardiac β-ARs remains elusive. Emerging evidence suggests that microtubule-dependent trafficking of mRNP (messenger ribonucleoprotein) and localized protein translation modulates protein compartmentation in cardiomyocytes. We hypothesized that β-AR compartmentation in cardiomyocytes is accomplished by selective trafficking of its mRNAs and localized translation. The localization pattern of β-AR mRNA was investigated using single molecule fluorescence in situ hybridization and subcellular nanobiopsy in rat cardiomyocytes. The role of microtubule on β-AR mRNA localization was studied using vinblastine, and its effect on receptor localization and function was evaluated with immunofluorescent and high-throughput Förster resonance energy transfer microscopy. An mRNA protein co-detection assay identified plausible β-AR translation sites in cardiomyocytes. The mechanism by which β-AR mRNA is redistributed post-heart failure was elucidated by single molecule fluorescence in situ hybridization, nanobiopsy, and high-throughput Förster resonance energy transfer microscopy on 16 weeks post-myocardial infarction and detubulated cardiomyocytes. β1AR and β2AR mRNAs show differential localization in cardiomyocytes, with β1AR found in the perinuclear region and β2AR showing diffuse distribution throughout the cell. Disruption of microtubules induces a shift of β2AR transcripts toward the perinuclear region. The close proximity between β2AR transcripts and translated proteins suggests that the translation process occurs in specialized, precisely defined cellular compartments. Redistribution of β2AR transcripts is microtubule-dependent, as microtubule depolymerization markedly reduces the number of functional receptors on the membrane. In failing hearts, both β1AR and β2AR mRNAs are redistributed toward the cell periphery, similar to what is seen in cardiomyocytes undergoing drug-induced detubulation. This suggests that t-tubule remodeling contributes to β-AR mRNA redistribution and impaired β2AR function in failing hearts. Asymmetrical microtubule-dependent trafficking dictates differential β1AR and β2AR localization in healthy cardiomyocyte microtubules, underlying the distinctive compartmentation of the 2 β-ARs on the plasma membrane. The localization pattern is altered post-myocardial infarction, resulting from transverse tubule remodeling, leading to distorted β2AR-mediated cyclic adenosine monophosphate signaling.

Abstract P2038: Role Of The Microtubule Network In Right Ventricle Passive Viscoelasticity With Pulmonary Hypertension Development

Microtubule (MT) polymerization is a key contributor to myocardium viscoelasticity, which describes elastic and viscous resistance under stress and impacts the contractile function. MT de- or hyper-polymerization has been shown to decrease or increase healthy cardiomyocyte viscoelasticity, but the responses of hypertrophied cells to these modifications are unknown. Moreover, the ventricular free wall is a complex tissue composed of myofibers, collagen and vasculature, and it exhibits anisotropic mechanical behavior. To fully understand the role of MT in the tissue-level anisotropic viscoelasticity of myocardium, we investigated the responses of healthy and failing rat right ventricles (RV) to alterations in MT network. All procedures were approved by Colorado State University IACUC. Adult male rats were treated with monocrotaline to induce pulmonary hypertension and RV failure. After euthanasia, the RV free wall underwent equibiaxial stress relaxation in intact state (baseline) and under the treatment of colchicine and deuterium oxide (D 2 O) to remove and enhance MT network, respectively. Viscoelastic parameters were quantified as previously described. As expected, the diseased RV had greater viscoelasticity than the healthy RV. Depolymerization of MT in healthy RVs reduced tissue viscosity (relaxation rate) and elasticity (relaxation modulus), and the changes were more significant in the longitudinal (outflow tract) direction. MT hyper-polymerization increased tissue elasticity and decreased viscosity, with the changes stronger in the circumferential direction. In diseased RVs, MT depolymerization reduced viscosity in both directions and elasticity only in the circumferential direction. However, MT hyper-polymerization unexpectedly decreased tissue elasticity and tended to decrease viscosity, as well. The altered MT polymerization dynamics after D 2 O treatment in a fibrotic environment may explain these heterogeneous responses This is the first report of distinct impacts of MT polymerization on the tissue mechanical behavior between the hypertrophied and healthy myocardium. The exact molecular mechanisms involving MT polymerization dynamics and the interactions with collagen await further investigation.

Exocytosis of Nanoparticles: A Comprehensive Review.

Both biomedical applications and safety assessments of manufactured nanomaterials require a thorough understanding of the interaction between nanomaterials and cells, including how nanomaterials enter cells, transport within cells, and leave cells. However, compared to the extensively studied uptake and trafficking of nanoparticles (NPs) in cells, less attention has been paid to the exocytosis of NPs. Yet exocytosis is an indispensable process of regulating the content of NPs in cells, which in turn influences, even decides, the toxicity of NPs to cells. A comprehensive understanding of the mechanisms and influencing factors of the exocytosis of NPs is not only essential for the safety assessment of NPs but also helpful for guiding the design of safe and highly effective NP-based materials for various purposes. Herein, we review the current status and progress of studies on the exocytosis of NPs. Firstly, we introduce experimental procedures and considerations. Then, exocytosis mechanisms/pathways are summarized with a detailed introduction of the main pathways (lysosomal and endoplasmic reticulum/Golgi pathway) and the role of microtubules; the patterns of exocytosis kinetics are presented and discussed. Subsequently, the influencing factors (initial content and location of intracellular NPs, physiochemical properties of NPs, cell type, and extracellular conditions) are fully discussed. Although there are inconsistent results, some rules are obtained, like smaller and charged NPs are more easily excreted. Finally, the challenges and future directions in the field have been discussed.

Changes in cell surface excess are coordinated with protrusion dynamics during 3D motility

To facilitate rapid changes in morphology without endangering cell integrity, each cell possesses a substantial amount of cell surface excess (CSE) that can be promptly deployed to cover cell extensions. CSE can be stored in different types of small surface projections such as filopodia, microvilli, and ridges, with rounded bleb-like projections being the most common and rapidly achieved form of storage. We demonstrate that, similar to rounded cells in 2D culture, rounded cells in 3D collagen contain large amounts of CSE and use it to cover developing protrusions. Upon retraction of a protrusion, the CSE this produces is stored over the cell body similar to the CSE produced by cell rounding. We present high-resolution imaging of F-actin and microtubules (MTs) for different cell lines in a 3D environment and demonstrate the correlated changes between CSE and protrusion dynamics. To coordinate CSE storage and release with protrusion formation and motility, we expect cells to have specific mechanisms for regulating CSE, and we hypothesize that MTs play a substantial role in this mechanism by reducing cell surface dynamics and stabilizing CSE. We also suggest that different effects of MT depolymerization on cell motility, such as inhibiting mesenchymal motility and enhancing amoeboid, can be explained by this role of MTs in CSE regulation.

Microtubule stabilization promotes the synthesis of type 2 collagen in nucleus pulposus cell by activating hippo-yap pathway.

Intervertebral disc degeneration (IDD) is the cardinal pathological mechanism that underlies low back pain. Mechanical stress of the intervertebral disc may result in a change in nucleus pulposus cells state, matrix degradation, and degeneration of the disc. Microtubules, which are components of the cytoskeleton, are involved in driving or regulating signal pathways, which sense and transmit mechano-transduction. Microtubule and the related proteins play an important role in the development of many diseases, while little is known about the role of microtubules in nucleus pulposus cells. Researchers have found that type II collagen (COL2) expression is promoted by microtubule stabilization in synovial mesenchymal stem cells. In this study, we demonstrated that microtubule stabilization promotes the expression of COL2 in nucleus pulposus cells. Stabilized microtubules stimulating Hippo signaling pathway, inhibiting YAP protein expression and activity. In addition, microtubules stabilization promotes the expression of COL2 and alleviates disc degeneration in rats. In summary, our study for the first time, identifies microtubule as a promising therapeutic target for IDD, up-regulating the synthesis of COL2 via Hippo-Yap pathway. Our findings may provide new insights into the etiologies and pathology for IDD, further, targeting of microtubule acetylation may be an effective strategy for the treatment of IDD.

The role of microtubules in microalgae: promotion of lipid accumulation and extraction

BackgroundMicrotubules in cells are closely related to the growth and metabolism of microalgae. To date, the study of microalgal microtubules has mainly concentrated on revealing the relationship between microtubule depolymerization and synthesis of precursors for flagellar regeneration. While information on the link between microtubule depolymerization and biosynthesis of precursors for complex organic matter (such as lipid, carbohydrate and protein), is still lacking, a better understanding of this could help to achieve a breakthrough in lipid regulation. With the aim of testing the assumption that microtubule disruption could regulate carbon precursors and redirect carbon flow to promote lipid accumulation, Chlorella sorokiniana SDEC-18 was pretreated with different concentrations of oryzalin.ResultsStrikingly, microalgae that were pretreated with 1.5 mM oryzalin accumulated lipid contents of 41.06%, which was attributed to carbon redistribution induced by microtubule destruction. To promote the growth of microalgae, two-stage cultivation involving microtubule destruction was employed, which resulted in the lipid productivity being 1.44 times higher than that for microalgae with routine single-stage cultivation, as well as yielding a desirable biodiesel quality following from increases in monounsaturated fatty acid (MUFA) content. Furthermore, full extraction of lipid was achieved after only a single extraction step, because microtubule destruction caused removal of cellulose synthase and thereby blocked cellulose biosynthesis.ConclusionsThis study provides an important advance towards observation of microtubules in microalgae through immunocolloidal gold techniques combined with TEM. Moreover, the observation of efficient lipid accumulation and increased cell fragility engendered by microtubule destruction has expanded our knowledge of metabolic regulation by microtubules. Finally, two-stage cultivation involving microtubule destruction has established ideal growth, coupling enhanced lipid accumulation and efficient oil extraction; thus gaining advances in both applied and fundamental research in algal biodiesel production.

Morphological Evidence for Novel Roles of Microtubules in Macrophage Phagocytosis

Although the phagocytic activity of macrophages has long been studied, the involvement of microtubules in the process is not well understood. In this study, we improved the fixation protocol and revealed a dynamically rearranging microtubule network in macrophages, consisting of a basal meshwork, thick bundles at the cell edge, and astral microtubules. Some astral microtubules extended beneath the cell cortex and continued to form bundles at the cell edge. These microtubule assemblies were mutually exclusive of actin accumulation during membrane ruffling. Although the stabilization of microtubules with paclitaxel did not affect the resting stage of the macrophages, it reduced the phagocytic activity and membrane ruffling of macrophages activated with serum-MAF, which induced rapid phagocytosis. In contrast, the destabilization of microtubules with nocodazole enhanced membrane ruffling and the internalization of phagocytic targets suggesting an inhibitory effect of the microtubule network on the remodeling of the actin network. Meanwhile, the microtubule network was necessary for phagosome maturation. Our detailed analyses of cytoskeletal filaments suggest a phagocytosis control system involving Ca2+ influx, the destabilization of microtubules, and activation of actin network remodeling, followed by the translocation and acidification of phagosomes on the microtubule bundles.

HY5 inhibits lateral root initiation in Arabidopsis through negative regulation of the microtubule-stabilizing protein TPXL5.

Tight control of lateral root (LR) initiation is vital for root system architecture and function. Regulation of cortical microtubule reorganization is involved in the asymmetric radial expansion of founder cells during LR initiation in Arabidopsis (Arabidopsis thaliana). However, critical genetic evidence on the role of microtubules in LR initiation is lacking and the mechanisms underlying this regulation are poorly understood. Here, we found that the previously uncharacterized microtubule-stabilizing protein TPX2-LIKE5 (TPXL5) participates in LR initiation, which is finely regulated by the transcription factor ELONGATED HYPOCOTYL5 (HY5). In tpxl5 mutants, LR density was decreased and more LR primordia (LRPs) remained in stage I, indicating delayed LR initiation. In particular, the cell width in the peripheral domain of LR founder cells after the first asymmetric cell division was larger in tpxl5 mutants than in the wild-type. Consistently, ordered transverse cortical microtubule arrays were not well generated in tpxl5 mutants. In addition, HY5 directly targeted the promoter of TPXL5 and downregulated TPXL5 expression. The hy5 mutant exhibited higher LR density and fewer stage I LRPs, indicating accelerated LR initiation. Such phenotypes were partially suppressed by TPXL5 knockout. Taken together, our data provide genetic evidence supporting the notion that cortical microtubules are essential for LR initiation and unravel a molecular mechanism underlying HY5 regulation of TPXL5-mediated microtubule reorganization and cell remodeling during LR initiation.

Amoebal Tubulin Cleavage Late during Infection Is a Characteristic Feature of Mimivirus but Not of Marseillevirus.

Mimivirus and Marseillevirus infections of Acanthamoeba castellanii, like most other viral infections, induce cytopathic effects (CPE). The details of how they bring about CPE and to what extent and how they modify the host cytoskeletal network are unclear. In this study, we compared the rearrangement of the host cytoskeletal network induced by Mimivirus and Marseillevirus upon infection. We show that while both Mimivirus and Marseillevirus infections of A. castellanii cells cause retraction of acanthopodia and depolymerization of the host actin filament network, the Mimivirus infection also results in characteristic cleavage of the host tubulin, a phenomenon not previously reported with any intracellular pathogens. Furthermore, we show that the amoebal tubulin cleavage during Mimivirus infection is a post-replicative event. Because time-lapse microscopy showed that Mimivirus infection leads to the bursting of cells, releasing the virus, we hypothesize that tubulin cleavage together with actin depolymerization during the later stages of Mimivirus assembly is essential for cell lysis due to apoptotic/necrotic cell death. We also characterize the Mimivirus-encoded gp560, a Zn metalloprotease, however, the purified gp560 protein was unable to cleave the commercially available porcine brain tubulin. While protein synthesis is essential for causing the morphological changes in the case of Mimivirus, the proteins which are packaged in the viral capsid along with the genome are sufficient to induce CPE in the case of Marseillevirus. IMPORTANCE In general, intracellular pathogens target the cytoskeletal network to enable their life cycle inside the host. Pathogen-induced changes in the host cell morphology usually accompany global changes in the cytoskeleton resulting in cytopathic effects. While viruses have been shown to use the host actin cytoskeleton for entry and transport during early infection, the role of microtubules in the viral life cycle is only beginning to emerge. Here, we show that the giant viruses Mimivirus and Marseillevirus both induce depolymerization of the actin filament, Mimivirus also causes a characteristic cleavage of tubulin not previously reported for any intracellular pathogen. Because tubulin cleavage occurs late during infection, we hypothesize that tubulin cleavage aids in cell death and lysis rather than establishing infection. The different strategies used by viruses with similar host niches may help them survive in competition.

Role of microtubules in neuro-electrical transmission

Unlike man-made electronic devices such as computers, the nervous system never suffers from “overheating” due to its massive neuro-electrical activities. This paper proposes a new hypothesis that neuronal microtubules (neuro-MTs), which are major structural components of axons and dendrites, are vacuum cylindrical nanotubes that can mediate electrical transmission with a unique form of quasi-superconductivity. It is speculated that hydrolysis of guanosine triphosphate catalyzed by the a-/ß-tubulin subunits would supply cellular energy to relocate electrons to form the conduction electrons inside neuro-MTs. Owing to the consecutive dipole ring structures of neuro-MTs, the moving speed of the conduction electrons inside neuro-MTs is expected to be very slow, and this feature would enable physiological neuro-electrical transmission with super-high energy efficiency. Further, the dipole ring structures of a neuro-MT would help terminate the electron conduction with high efficiency. The proposed neuro-MT-mediated electrical transmission offers a new mechanistic explanation for the saltatory conduction of action potentials along the axons. Lastly, it is speculated that owing to its unique consecutive dipole sheet structures, the myelin sheath which wraps around large axons and some dendrites, may functionally serve as an effective shield for the electromagnetic fields generated by the conduction electrons inside the axonal neuro-MTs.

The circadian system in cystic fibrosis mice is regulated by histone deacetylase 6.

Disordered sleep experienced by people with cystic fibrosis (CF) suggest a possible disruption in circadian regulation being associated with the loss of cystic fibrosis transmembrane conductance regulator (Cftr) function. To test this hypothesis, circadian regulation was assessed in an F508del/F508del CF mouse model. CF mice exhibited significant alterations in both timing of locomotor activity and in mean activity per hour in both light-dark (LD) and dark-dark (DD) photoperiods compared with wild-type (WT) controls. It was also noted that in DD periodicity increased in CF mice, whereas shortening in WT mice as is expected. CF mice also exhibited altered timing of circadian gene expression and a reduction of melatonin production at all time points. Mechanistically, the role of microtubules in regulating these outcomes was explored. Mice lacking expression of tubulin polymerization promoting protein (Tppp) effectively mimicked CF mouse phenotypes with each measured outcome. Depleting expression of the microtubule regulatory protein histone deacetylase 6 (Hdac6) from CF mice (CF/Hdac6) resulted in the reversal of each phenotype to WT profiles. These data demonstrate an innate disruption of circadian regulation in CF mice and identify a novel microtubule-related mechanism leading to this disruption that can be targeted for therapeutic intervention.

Microtubules as Regulators of Neural Network Shape and Function: Focus on Excitability, Plasticity and Memory.

Neuronal microtubules (MTs) are complex cytoskeletal protein arrays that undergo activity-dependent changes in their structure and function as a response to physiological demands throughout the lifespan of neurons. Many factors shape the allostatic dynamics of MTs and tubulin dimers in the cytosolic microenvironment, such as protein–protein interactions and activity-dependent shifts in these interactions that are responsible for their plastic capabilities. Recently, several findings have reinforced the role of MTs in behavioral and cognitive processes in normal and pathological conditions. In this review, we summarize the bidirectional relationships between MTs dynamics, neuronal processes, and brain and behavioral states. The outcomes of manipulating the dynamicity of MTs by genetic or pharmacological approaches on neuronal morphology, intrinsic and synaptic excitability, the state of the network, and behaviors are heterogeneous. We discuss the critical position of MTs as responders and adaptative elements of basic neuronal function whose impact on brain function is not fully understood, and we highlight the dilemma of artificially modulating MT dynamics for therapeutic purposes.

The legacy of kinesins in the pollen tube 30 years later.

The pollen tube is fundamental in the reproduction of seed plants. Particularly in angiosperms, we now have much information about how it grows, how it senses extracellular signals, and how it converts them into a directional growth mechanism. The expansion of the pollen tube is also related to dynamic cytoplasmic processes based on the cytoskeleton (such as polymerization/depolymerization of microtubules and actin filaments) or motor activity along with the two cytoskeletal systems and is dependent on motor proteins. While a considerable amount of information is available for the actomyosin system in the pollen tube, the role of microtubules in the transport of organelles or macromolecular structures is still quite uncertain despite that 30 years ago the first work on the presence of kinesins in the pollen tube was published. Since then, progress has been made in elucidating the role of kinesins in plant cells. However, their role within the pollen tube is still enigmatic. In this review, I will postulate some roles of kinesins in the pollen tube 30 years after their initial discovery based on information obtained in other plant cells in the meantime. The most concrete hypotheses predict that kinesins in the pollen tube enable the short movement of specific organelles or contribute to generative cell or sperm cell transport, as well as mediate specific steps in the process of endocytosis.

Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing Centers.

Zika virus (ZIKV) became a global health concern in 2016 due to its links to congenital microcephaly and other birth defects. Flaviviruses, including ZIKV, reorganize the endoplasmic reticulum (ER) to form a viroplasm, a compartment where virus particles are assembled. Microtubules (MTs) and microtubule-organizing centers (MTOCs) coordinate structural and trafficking functions in the cell, and MTs also support replication of flaviviruses. Here we investigated the roles of MTs and the cell’s MTOCs on ZIKV viroplasm organization and virus production. We show that a toroidal-shaped viroplasm forms upon ZIKV infection, and MTs are organized at the viroplasm core and surrounding the viroplasm. We show that MTs are necessary for viroplasm organization and impact infectious virus production. In addition, the centrosome and the Golgi MTOC are closely associated with the viroplasm, and the centrosome coordinates the organization of the ZIKV viroplasm toroidal structure. Surprisingly, viroplasm formation and virus production are not significantly impaired when infected cells have no centrosomes and impaired Golgi MTOC, and we show that MTs are anchored to the viroplasm surface in these cells. We propose that the viroplasm is a site of MT organization, and the MTs organized at the viroplasm are sufficient for efficient virus production.