Multifunctional Compartment Research Articles

Lysosomes: multifunctional compartments ruled by a complex regulatory network

More than 50 years have passed since Nobel laureate Cristian de Duve described for the first time the presence of tiny subcellular compartments filled with hydrolytic enzymes: the lysosome. For a long time, lysosomes were deemed simple waste bags exerting a plethora of hydrolytic activities involved in the recycling of biopolymers, and lysosomal genes were considered to just be simple housekeeping genes, transcribed in a constitutive fashion. However, lysosomes are emerging as multifunctional signalling hubs involved in multiple aspects of cell biology, both under homeostatic and pathological conditions. Lysosomes are involved in the regulation of cell metabolism through the mTOR/TFEB axis. They are also key players in the regulation and onset of the immune response. Furthermore, it is becoming clear that lysosomal hydrolases can regulate several biological processes outside of the lysosome. They are also implicated in a complex communication network among subcellular compartments that involves intimate organelle‐to‐organelle contacts. Furthermore, lysosomal dysfunction is nowadays accepted as the causative event behind several human pathologies: low frequency inherited diseases, cancer, or neurodegenerative, metabolic, inflammatory, and autoimmune diseases. Recent advances in our knowledge of the complex biology of lysosomes have established them as promising therapeutic targets for the treatment of different pathologies. Although recent discoveries have started to highlight that lysosomes are controlled by a complex web of regulatory networks, which in some cases seem to be cell‐ and stimuli‐dependent, to harness the full potential of lysosomes as therapeutic targets, we need a deeper understanding of the little‐known signalling pathways regulating this subcellular compartment and its functions.

Multifunctional Integrated Compartment Systems for Incompatible Cascade Reactions Based on Onion-Like Photonic Spheres.

One of the central aims of synthetic biology and metabolic engineering is to mimic the integrality of eukaryotic cells to construct a multifunctional compartment system to perform multistep incompatible cascade reactions in a one-pot, controlled, and selective fashion. The key challenge is how to address the coexistence of antagonistic reagents and to incorporate these functionalities into an integrated system in a smart and efficient way. A novel strategy called "iterative etching-grafting" is proposed here based on monodispersed photonic spheres (PSs) prepared by microfluidics, which constructs a universal platform for incompatible cascade reactions. As a proof of concept, we spatiotemporally regulated the degree of etching of PSs, then grafted precursory groups of acid and base onto PSs, and incorporated a photocleavage method, which were capable of compartmentalizing the acid and base inside PSs. Utilizing the band-gap offsets of PSs could track the progress of cascade reactions in situ, and grafting various charged polymers on the surface of the pores by surface-initiated atom transfer radical polymerization (SI-ATRP) achieved the selectivity of the substrates, which flexibly constructed a multifunctional and integrated acid-base photonic multicompartment system (PMCS). The created PMCS shows excellent catalytic performance, convenient monitoring, and efficient substrate selectivity in the deacetalization-Knoevenagel cascade reaction. Furthermore, two types of electrophile/nucleophile PMCSs have also been accessibly constructed, demonstrating the facile generation of other incompatible systems with the versatility as well as the advancement and extensibility of the developed strategy.

Rab8a localisation and activation by Toll-like receptors on macrophage macropinosomes.

Macropinocytosis is a prevalent and essential pathway in macrophages where it contributes to anti-microbial responses and innate immune cell functions. Cell surface ruffles give rise to phagosomes and to macropinosomes as multi-functional compartments that contribute to environmental sampling, pathogen entry, plasma membrane turnover and receptor signalling. Rapid, high resolution, lattice light sheet imaging demonstrates the dynamic nature of macrophage ruffling. Pathogen-mediated activation of surface and endosomal Toll-like receptors (TLRs) in macrophages upregulates macropinocytosis. Here, using multiple forms of imaging and microscopy, we track membrane-associated, fluorescently-tagged Rab8a expressed in live macrophages, using a variety of cell markers to demonstrate Rab8a localization and its enrichment on early macropinosomes. Production of a novel biosensor and its use for quantitative FRET analysis in live cells, pinpoints macropinosomes as the site for TLR-induced activation of Rab8a. We have previously shown that TLR signalling, cytokine outputs and macrophage programming are regulated by the GTPase Rab8a with PI3 Kγ as its effector. Finally, we highlight another effector, the phosphatase OCRL, which is located on macropinosomes and interacts with Rab8a, suggesting that Rab8a may operate on multiple levels to modulate phosphoinositides in macropinosomes. These findings extend our understanding of macropinosomes as regulatory compartments for innate immune function in macrophages. This article is part of the Theo Murphy meeting issue 'Macropinocytosis'.

Dynamic Docking and Undocking Processes Addressing Selectively the Outside and Inside of Polymersomes.

Increasing complexity and diversity of polymersomes and their compartments is a key issue for mimicking cellular functions and protocells. Thus, new challenges arise in terms of achieving tunable membrane permeability and combining it with control over the membrane diffusion process, and thus enabling a localized and dynamic control of functionality and docking possibilities within or on the surface of polymeric compartments. This study reports the concept of polymersomes with pH-tunable membrane permeability for controlling sequential docking and undocking processes of small molecules and nanometer-sized protein mimics selectively on the inside and outside of the polymersome membrane as a further step toward the design of intelligent multifunctional compartments for use in synthetic biology and as protocells. Host-guest interactions between adamantane and β-cyclodextrin as well as noncovalent interactions between poly(ethylene glycol) tails and β-cyclodextrin are used to achieve selective and dynamic functionalization of the inner and outer spheres of the polymersome membrane.

Self-Assembly of Smart Multifunctional Hybrid Compartments with Programmable Bioactivity

Artificial microcompartments are highly desirable for understanding the mechanism of formation of primitive cells for the origin of life and have technological effects in broad fields such as materials science, catalysis, environmental remediation, biomedicine, and biotechnology. However, it remains a critical challenge for the construction of a structurally stable, semipermeable, and multifunctional compartment that can maintain a protective and confined internal space while allowing internalization of ingredients. Here, we present a strategy for construction of novel smart multifunctional hybrid compartments (SMHCs) with semipermeability, stimulus-response, and enzymatic bioactivity. The smart compartments were assembled by packing magnetic nanoparticles on oil/water interface, and the interstitial pores were gated by designed thermosensitive copolymer brushes. The materials characterization, multifunctionality, and on-demand permeability of prepared hybrid compartments were investigated. Notably, biolo...

Versatility of the green microalga cell vacuole function as revealed by analytical transmission electron microscopy.

Vacuole is a multifunctional compartment central to a large number of functions (storage, catabolism, maintenance of the cell homeostasis) in oxygenic phototrophs including microalgae. Still, microalgal cell vacuole is much less studied than that of higher plants although knowledge of the vacuolar structure and function is essential for understanding physiology of nutrition and stress tolerance of microalgae. Here, we combined the advanced analytical and conventional transmission electron microscopy methods to obtain semi-quantitative, spatially resolved at the subcellular level information on elemental composition of the cell vacuoles in several free-living and symbiotic chlorophytes. We obtained a detailed record of the changes in cell and vacuolar ultrastructure in response to environmental stimuli under diverse conditions. We suggested that the vacuolar inclusions could be divided into responsible for storage of phosphorus (mainly in form of polyphosphate) and those accommodating non-protein nitrogen (presumably polyamine) reserves, respectively.The ultrastructural findings, together with the data on elemental composition of different cell compartments, allowed us to speculate on the role of the vacuolar membrane in the biosynthesis and sequestration of polyphosphate. We also describe the ultrastructural evidence of possible involvement of the tonoplast in the membrane lipid turnover and exchange of energy and metabolites between chloroplasts and mitochondria. These processes might play a significant role in acclimation in different stresses including nitrogen starvation and extremely high level of CO2 and might also be of importance for microalgal biotechnology. Advantages and limitations of application of analytical electron microscopy to biosamples such as microalgal cells are discussed.

From antibodies to adiponectin: role of ERp44 in sizing and timing protein secretion

A large fraction of the proteome is synthesized and folded in the endoplasmic reticulum (ER), a multifunctional compartment also playing pivotal roles in Ca(2+) storage, redox homeostasis and signalling. From the ER, secretory proteins begin their journey towards their final destinations, the organelles of the exocytic and endocytic compartments, the plasma membrane or the extracellular space. Fidelity of protein-based intracellular communication is guaranteed by quality control (QC) mechanisms located at the ER-Golgi interface, which restrict forward transport to native proteins. QC is used also to time or shape the secretome. Furthermore, professional secretory cells face a problem of quantity, as well as quality of their protein products. This essay summarizes recent findings that identify ERp44 as a key regulator of protein secretion, Ca(2+) signalling and redox regulation.

The role of the plant nucleolus in pre-mRNA processing.

The nucleolus is a multifunctional compartment of the eukaryotic nucleus. Besides its well-recognised role in transcription and processing of ribosomal RNA and the assembly of ribosomal subunits, the nucleolus has functions in the processing and assembly of a variety of RNPs and is involved in cell cycle control and senescence and as a sensor of stress. Historically, nucleoli have been tenuously linked to the biogenesis and, in particular, export of mRNAs in yeast and mammalian cells. Recently, data from plants have extended the functions in which the plant nucleolus is involved to include transcriptional gene silencing as well as mRNA surveillance and nonsense-mediated decay, and mRNA export. The nucleolus in plants may therefore have important roles in the biogenesis and quality control of mRNAs.

Functions of the Vacuole in Higher Plant Cells

Current views of the activities inherent in the vacuole as a multifunctional compartment in higher plant cells are outlined. The available data indicate that the vacuole is involved in ion homeostasis of the cytosol, storing products of the primary and secondary metabolism, osmoregulation, generation of defense responses of plant cells under biotic and abiotic stress, and programmed cell death. Transport of diverse molecules and ions across the vacuolar membrane, i.e., the tonoplast, plays the major role in all these functional activities of the vacuole. Much progress toward the identification of the transport systems located in this membrane and the elucidation of the mechanisms underlying their functioning has been achieved in the last 10–15 years and has given new insights into the role of the vacuole in the integration and regulation of plant cell metabolism.

Development and molecular organization of dendritic spines and their synapses.

Nearly all excitatory input in the hippocampus impinges on dendritic spines which serve as multifunctional compartments that can, at the very least, selectively isolate and amplify incoming signals. Their importance to normal brain function is highlighted by the severe mental impairment observed in most individuals having poorly developed spines (Purpura, Science 1974;186:1126-1128). Distinct groups of membrane proteins, cytoskeletal elements, scaffolding proteins, and second messenger-related proteins are concentrated particularly in dendritic spines, but their ability to generate, maintain, and coordinately regulate spine structure or function is poorly understood. Here we review the unique molecular composition of dendritic spines along with the factors known to influence dendritic spine development in order to construct a model of dendritic spine development in relation to synaptogenesis.

Development and molecular organization of dendritic spines and their synapses

Nearly all excitatory input in the hippocampus impinges on dendritic spines which serve as multifunctional compartments that can, at the very least, selectively isolate and amplify incoming signals. Their importance to normal brain function is highlighted by the severe mental impairment observed in most individuals having poorly developed spines (Purpura, Science 1974;186:1126–1128). Distinct groups of membrane proteins, cytoskeletal elements, scaffolding proteins, and second messenger-related proteins are concentrated particularly in dendritic spines, but their ability to generate, maintain, and coordinately regulate spine structure or function is poorly understood. Here we review the unique molecular composition of dendritic spines along with the factors known to influence dendritic spine development in order to construct a model of dendritic spine development in relation to synaptogenesis. Hippocampus 2000;10:512–526. © 2000 Wiley-Liss, Inc.

Processing of endogenous pre-mRNAs in association with SC-35 domains is gene specific.

Analysis of six endogenous pre-mRNAs demonstrates that localization at the periphery or within splicing factor-rich (SC-35) domains is not restricted to a few unusually abundant pre-mRNAs, but is apparently a more common paradigm of many protein-coding genes. Different genes are preferentially transcribed and their RNAs processed in different compartments relative to SC-35 domains. These differences do not simply correlate with the complexity, nuclear abundance, or position within overall nuclear space. The distribution of spliceosome assembly factor SC-35 did not simply mirror the distribution of individual pre-mRNAs, but rather suggested that individual domains contain both specific pre-mRNA(s) as well as excess splicing factors. This is consistent with a multifunctional compartment, to which some gene loci and their RNAs have access and others do not. Despite similar molar abundance in muscle fiber nuclei, nascent transcript "trees" of highly complex dystrophin RNA are cotranscriptionally spliced outside of SC-35 domains, whereas posttranscriptional "tracks" of more mature myosin heavy chain transcripts overlap domains. Further analyses supported that endogenous pre-mRNAs exhibit distinct structural organization that may reflect not only the expression and complexity of the gene, but also constraints of its chromosomal context and kinetics of its RNA metabolism.

Multifunctional compartments in the nucleus: Insights from DNA and RNA localization

Multifunctional compartments in the nucleus: Insights from DNA and RNA localization

Multifunctional compartments in the nucleus: Insights from DNA and RNA localization

Journal of Cellular BiochemistryVolume 62, Issue 2 p. 181-190 Prospects Multifunctional compartments in the nucleus: Insights from DNA and RNA localization Christine Moulton Clemson, Christine Moulton Clemson Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655Search for more papers by this authorJeanne Bentley Lawrence, Corresponding Author Jeanne Bentley Lawrence Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655.Search for more papers by this author Christine Moulton Clemson, Christine Moulton Clemson Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655Search for more papers by this authorJeanne Bentley Lawrence, Corresponding Author Jeanne Bentley Lawrence Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655.Search for more papers by this author First published: August 1996 https://doi.org/10.1002/(SICI)1097-4644(199608)62:2<181::AID-JCB6>3.0.CO;2-OCitations: 32AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume62, Issue2August 1996Pages 181-190 RelatedInformation