AlphaB-crystallin modified by methylglyoxal prevents fibrillization of α-synuclein A53T.

Climate change and environmental pollution are two primary challenges facing biodiversity and ecosystem stability. Earthworms are key contributors to soil structure and nutrient cycling, and their molecular stress responses can provide an early indication of soil health impairment. Heat shock proteins are central to the stress response, and small heat shock proteins (sHSPs) are ATP-independent chaperones that limit stress-induced protein aggregation. Because their expression is stress-sensitive, sHSPs are promising molecular markers for soil stress and contributors to thermotolerance. Eisenia fetida, a widely used ecotoxicology model, relies on molecular chaperones like small heat shock proteins (sHSPs) for stress tolerance. We previously characterized sHSPs containing a single α-crystallin domain (ACD) in E. fetida. Here, we report the first identification of sHSPs containing two α-crystallin domains (ACDs) in annelid species. These genes were identified from an E. fetida transcriptome, their domain architecture was defined, and their transcriptional responses were quantified under heat stress, desiccation, and exposure to two pollutants (bisphenol A and endosulfan), including combined exposure with elevated temperature. Double-ACD sHSPs showed stimulus- and time-dependent transcriptional patterns. Moderate heat and desiccation primarily induced late (24h) upregulation of several sHSP genes, whereas bisphenol A at optimal temperature did not result in significant transcriptional change and endosulfan produced only limited changes under single-stressor exposure. In contrast, combined exposure to endosulfan and elevated temperature triggered a significant upregulation of multiple sHSP genes, consistent with an additive stress effect. These results expand this protein family diversity in annelids and support a staged sHSP response in which structurally distinct sHSPs may contribute to resilience under prolonged or combined environmental stress.

Extreme high temperatures significantly threaten insect development and reproduction. Small heat shock proteins (sHSPs) are crucial for thermal adaptation, but their specific roles in reproduction and heat stress response remain incompletely understood. This study investigates SfHSP19.8, a testis-enriched sHSP in the fall armyworm (Spodoptera frugiperda), to elucidate its function. Testis-specific expression of SfHSP19.8 occurred during the 6th- instar larval and pupal stages. Homozygous knockout mutants were generated using CRISPR/Cas9 technology. Transcriptomic analysis of 6th-instar larval testes revealed dysregulation of genes in steroid hormone biosynthesis and detoxification pathways. However, knockout did not impair adult male fertility, testis morphology or sperm count under standard conditions. SfHSP19.8 expression was strongly induced by heat shock across developmental stages. Mutants exhibited severely compromised thermotolerance under heat stress, including complete egg hatching failure, high larval mortality, prolonged larval development, and reduced adult longevity and reproductive fitness. These findings demonstrate that SfHSP19.8 is essential for systemic thermotolerance across life stages and maintains reproductive function specifically under thermal challenge, while being dispensable for basal male reproduction under optimal conditions. SfHSP19.8 represents a potential target for pest control strategies in the context of future climate warming. © 2026 Society of Chemical Industry.

Genome-wide identification and functional validation of thermal tolerance genes in Mytilus coruscus using a yeast-based functional screening system.

Small heat shock protein HSPB8 interacts with a pre-fibrillar TDP43 low complexity domain species to delay fibril formation.

Abstract Background Dilated cardiomyopathy (DCM) is a major cause of heart failure in young patients, with a genetic aetiology identified in up to 40% of cases. Variants in *CRYAB*, encoding the small heat shock protein αB-crystallin, are rare but increasingly recognized in inherited cardiomyopathies. Case summary We report a 16-year-old male who presented with progressive heart failure symptoms and palpitations. Transthoracic echocardiography revealed a dilated left ventricle with severely reduced systolic function. Holter monitoring documented episodes of ventricular tachycardia. Cardiac magnetic resonance demonstrated global biventricular systolic dysfunction and focal mid-wall late gadolinium enhancement in the interventricular septum. Genetic testing identified a novel heterozygous *CRYAB* variant (p.Arg69Cys), confirmed by Sanger sequencing, together with a *PSEN2* variant of uncertain significance. The patient was treated with guideline-directed medical therapy for heart failure and underwent prophylactic implantable cardioverter–defibrillator implantation. Clinical status and left ventricular function improved during follow-up. Discussion This case highlights the importance of integrating advanced cardiac imaging and genetic testing in young patients with unexplained DCM and malignant ventricular arrhythmias. Novel *CRYAB* variants may be associated with early-onset DCM and arrhythmic risk, influencing prognostic assessment and management.

Both autophagy and heat shock proteins (HSPs) play dual roles in viral infections, yet their coordination in antiviral defense remains unclear. Here, we show that a cytosolic small heat shock protein (AcsHSP) and a type II J-domain protein (AcDNAJB13) from areca palm interact with the coat protein (CP) of areca palm velarivirus 1 (APV1) independently of HSP70 chaperones. Their closest Nicotiana benthamiana homologs also bind CP. Both APV1 infection and CP expression induces the transcription of sHSP and DNAJB13, which in turn inhibits CP accumulation. Silencing of these genes enhances APV1 infection and CP accumulation, while overexpression of AcsHSP reduces viral accumulation. Mechanistically, CP is degraded via autophagy. Both AcsHSP and AcDNAJB13 interact with the autophagosome marker ATG8f1. However, AcsHSP strengthens CP-ATG8f1 binding, whereas AcDNAJB13 weakens it. These findings reveal distinct yet complementary mechanisms by which sHSP and DNAJB13 coordinate with autophagy to restrict viral infection.

To better understand the mechanisms of 5-hydroxytryptamine receptor 4 (HTR4)-mediated vasorelaxation, lateral saphenous veins from cattle (n = 4 to 7) were collected and assessed for vasoactivity in response to increasing concentrations of a selective HTR4 agonist (BIMU 8) in the absence and presence of inhibitors selective for downstream proteins involved with cyclic nucleotide-mediated signaling. Vessels were pre-contracted with 1 × 10-4 M phenylephrine and exposed to increasing HTR4 agonist concentrations. Vasoactive response data were normalized as a percentage of the maximum contractile response induced by the phenylephrine pre-contraction. Antagonism of HTR4 attenuated the vasorelaxation induced by BIMU 8. Removal of the endothelium did not influence HTR4 mRNA expression, HTR4 protein expression, or HTR4-mediated vasorelaxation. In the presence of inhibitors selective for adenylate cyclase or guanylate cyclase, 66% and 87% of the maximal HTR4-mediated vasorelaxation response was attenuated. In the presence of inhibitors selective for protein kinase A or protein kinase G, 66% and 98% of the maximal HTR4-mediated vasorelaxation response was attenuated. In the presence of non-selective blockers of Ca2+ and K+ channels, 65% and 64% of the maximal HTR4-mediated vasorelaxation response was attenuated. In the presence of inhibitors selective for myosin light chain phosphatase and small heat shock protein phosphorylation, 72% and 57% of the maximal HTR4-mediated vasorelaxation response was attenuated. HTR4-mediated vasorelaxation occurs through an endothelium-independent, cyclic nucleotide-dependent mechanism. Downstream proteins involved in the signaling cascade leading to vasorelaxation include protein kinase A and G, Ca2+ channels, K+ channels, myosin light chain phosphatase, and small heat shock proteins.

The tick Haemaphysalis longicornis is a major vector for several zoonotic pathogens, including Rickettsia heilongjiangensis. Small heat-shock proteins (sHSPs) are critical for stress responses and host-pathogen interactions. Among them, the HSP20 gene was found upregulated during rickettsial infection, whereas its specific function at the host-pathogen interface remains undefined. The full length of the HSP20 gene (HlHSP20) and its expression profile was characterized in H. longicornis, and RNA interference (RNAi) was used to knockdown HlHSP20, followed by the quantification of R. heilongjiangensis proliferation. Proteins from R. heilongjiangensis interacting with HlHSP20 were identified using GST pulldown coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and validated by yeast two-hybrid (Y2H) assays. HlHSP20 is a conserved, non-transmembrane intracellular sHSP with a αB-crystallin domain, showing the highest expression in egg and larval stages. The knockdown of HlHSP20 significantly promoted the proliferation of R. heilongjiangensis, and interaction screening revealed that HlHSP20 specifically binds to the 50S ribosomal protein L14 (RhRPL14) of R. heilongjiangensis. The present study demonstrates that HlHSP20 acts as a host restriction factor against R. heilongjiangensis in H. longicornis, likely through a direct interaction with the pathogen ribosome protein. This work unveils a novel component of the antimicrobial defense of ticks and identifies HlHSP20 as a potential target for disrupting rickettsial transmission.

Y. Sun and T. H. MacRae, "Characterization of novel sequence motifs within N- and C-terminal extensions of p26, a small heat shock protein from Artemia franciscana," The FEBS Journal 272, no. 20 (2005): 5230-5243, doi:https://doi.org/10.1111/j.1742-4658.2005.04920.x. The above article, first published on 7 October 2005 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief; the Federation of European Biochemical Societies; and John Wiley & Sons Ltd. The retraction has been agreed upon following an investigation into concerns initially raised by a third party on PubPeer [1], which revealed several instances of apparent data manipulation in Fig. 3C-G, 3C-R of the article. An investigation performed by the publisher confirmed these findings and uncovered additional apparent data manipulation in Figs 2A,D, 3B and 4. As raw data were not available for inspection, the editors have lost confidence in the results presented in this paper and have decided to retract the study. The corresponding author's institution cooperated with the investigation and has been notified of the retraction. Author T. H. MacRae could not be contacted because he is now deceased. Author Y. Sun did not respond to communications during the investigation and was informed of the retraction. Reference [1] Yong-Chang Zhou and Illex illecebrosus, Comments on "Characterization of novel sequence motifs within N-and C-terminal extensions of p26, a small heat shock protein from Artemia franciscana," PubPeer, October 2025. https://pubpeer.com/publications/3DD2D5069DC67E960CE75091D61853.

Molecular, cellular, and clinical aspects of myofibrillar myopathy caused by HSPB8 frameshift mutations.

Small heat shock proteins in plants: Structure, function and role in stress adaptation.

The small heat shock protein HSP17.2B is an essential component for HDS-mediated thermotolerance in Physcomitrium patens.

CryAB-driven amyloidogenesis in Drosophila muscle engages extracellular vesicle pathways for cellular release.

Deception Island fumaroles in Antarctica represent rare environments where extreme heat intersects with cryospheric and marine conditions, creating remarkable environmental gradients. From the near-boiling sediments, we reconstructed a high-quality metagenome-assembled genome affiliated with the Pyrodictiaceae. Phylogenomic analyses revealed that this genome, proposed to represent Ca. Pyroantarcticum pellizari, forms a distinct lineage separated from known genera in the family. Functional annotation uncovered a versatile metabolic repertoire, including pathways for sulfur and nitrogen cycling, peptide and amino acid transport, and mixotrophic energy conservation. Stress-response systems such as reverse gyrase, thermosome, and small heat-shock proteins were complemented by lineage-specific genes related to membrane stability, metal detoxification, and Pyrodictiaceae-specific cannulae. These adaptations likely support survival under sharp temperature gradients, hydrogen sulfide emissions, and high metal concentrations at the volcanic-cryosphere-marine interface. Our findings expand the phylogenetic and ecological scope of Pyrodictiaceae, highlighting Antarctic marine volcanoes as unique refuges for hyperthermophiles and as valuable models for investigating life's habitability under extreme temperatures.

As Earth’s temperature rises, fungal pathogens are adapting, altering host-pathogen interactions, disease patterns, and response to the antimicrobial drugs. Here, we show that thermal adaptation to 42°C leads to reversible changes in fungal colony size, appearance, and azole drug response in the human pathogenic fungusAspergillus fumigatus. Importantly, this adaptation is mediated by a lncRNA,afu-182,whose RNA levels negatively correlate with temperature. Growth at a lower temperature or ectopic upregulation ofafu-182RNA levels reverses the temperature adaptation. Global transcriptomic analyses show an enrichment of pathogenesis-associated genes at 37°C and 42°C compared to 25°C. Interestingly, we found that small heat shock proteins and chaperones, but not ATP-dependent heat-shock proteins, are negatively regulated byafu-182at 37°C and 42°C at transcriptional level. Previously, we have shown that Δafu-182strains produce worse disease outcomes in a murine model of invasive pulmonary aspergillosis (IPA). Here, more importantly, we show that the overexpression ofafu-182in clinically azole-resistant isolates increased survival in a murine model of IPA. Taken together, fungal adaptation to increased temperature leads to a decrease inafu-182RNA levels that is associated with worse disease outcomes upon azole treatment. This provides a framework to take temperature into account when analyzing the rise in azole MIC in environmental and clinical isolates.Significance statementAspergillus fumigatusis the causative agent of most mold associated infections and can tolerate temperatures above 50°C. A lncRNA levels negatively correlate with increasing temperature, and this increases the fungi’s ability to tolerate azole drugs bothin vitroandin vivo. Changing the levels ofafu-182improves anti-fungal treatment outcomes.

TAR DNA-binding protein 43 (TDP-43) is a nucleic acid-binding protein that regulates processes of mRNA metabolism, during which it undergoes condensation mediated by its C-terminal low-complexity domain (TDP-43LCD). TDP-43 aggregation and condensation are associated with neurodegenerative disease. However, the proteostasis mechanisms that regulate these processes remain elusive. Some evidence has shown that the molecular chaperone small heat shock protein HspB1 binds to and regulates the cytoplasmic phase separation of TDP-43, indicating that other small heat shock proteins may have similar effects. Here, we demonstrate divergent behaviors for HspB1 and its homolog HspB5 on TDP-43LCD condensation and aggregation. In addition to inhibiting TDP-43LCD aggregation, HspB1 partitions into TDP-43LCD condensates and increases the dynamic exchange of TDP-43LCD within condensates and with the surrounding solution. Phosphorylation-mimicking mutations within HspB1 enhance these effects. HspB5 inhibits TDP-43LCD aggregation more effectively than HspB1 and partitions into TDP-43LCD condensates, where it delays the pathological transition of the condensate to a gel/solid. We identify the N- and C-terminal regions of HspB1 and HspB5 to be crucial for the chaperone effects, and highlight the role of sequence diversity within these regions in defining small heat shock protein function. These findings demonstrate that HspB1 and HspB5 are regulators of TDP-43 phase separation and aggregation and may be potential therapeutic targets in mitigating toxic TDP-43 aggregation in neurodegenerative disease.

Sugarcane mosaic virus (SCMV) causes substantial yield losses worldwide, yet the molecular basis underlying resistance and susceptibility in sugarcane remains incompletely understood. Here, we performed time-resolved transcriptome profiling of two contrasting sugarcane genotypes, the SCMV-susceptible cultivar Badila and its resistant somatic mutant FG1, across five infection stages. Absolute quantification revealed rapid viral RNA replication in Badila, whereas FG1 showed early suppression followed by SCMV clearance. Comparative transcriptomic analyses showed that FG1 mounted a rapid and sustained defence-associated transcriptional response, whereas Badila displayed delayed, predominantly repressive gene expression changes. Weighted gene co-expression network analysis identified gene modules strongly correlated with viral RNA levels and highlighted the small heat shock protein gene ScHSP17.5 as a central hub associated with susceptibility. Protein-protein interaction assays demonstrated that ScHSP17.5 and ScHSP17.9A specifically interact with the SCMV movement protein P3N-PIPO, but not with P3 or the coat protein. Functional assays in Nicotiana benthamiana further showed that overexpression of either ScHSP enhanced SCMV RNA replication, with co-expression producing a synergistic effect. Together, these results support a model in which SCMV exploits host small heat shock proteins via P3N-PIPO to promote viral accumulation, whereas early redox- and signalling-associated responses restrict infection in resistant sugarcane. This study provides mechanistic insight into SCMV-host interactions and identifies candidate targets for resistance breeding.

Small heat shock proteins (sHSPs) act as molecular chaperones that protect other proteins from damage caused by stress-induced denaturation. Bermudagrass (Cynodon dactylon L.) is a broadly adopted forage and turfgrass known for its capability to withstand various abiotic stresses. However, the biological pathways by which sHSPs promote drought tolerance in bermudagrass remain unclear. In this study, 99 sHSPs were characterized in the bermudagrass genome. Drought stress led to the induction of the majority of these genes with CdsHSP16.970 showing the most significant induction. Overexpression (OE) of CdsHSP16.970 promoted root elongation and improved seedling growth performance in transgenic Arabidopsis lines under osmotic stress, with reduced electrolyte leakage (EL) and lower malondialdehyde (MDA) deposition compared with the control. Meanwhile, several stress-related genes were significantly induced in CdsHSP16.970-OE plants when subjected to osmotic stress compared to the control group. Two basic leucine zipper transcription factors, CdbZIP04 and CdbZIP65, were also induced by drought stress in bermudagrass. Further investigation using electrophoretic mobility shift assay, yeast one-hybrid and dual-LUC assays revealed that they directly and specifically bind to the upstream regulatory region of CdsHSP16.970, consequently promoting its expression. In summary, our results suggest that the CdbZIPs-CdsHSP16.970 cascade positively regulates the osmotic stress signaling pathway in bermudagrass.

ABSTRACT Heat shock proteins (HSPs) are highly conserved molecular chaperones that maintain proteostasis under environmental and physiological stress. In aquaculture research, HSP responses have been studied primarily in relation to temperature, salinity, pollutants, and pathogens in juvenile and adult stages, whereas the nutritional regulation of HSP dynamics during early larval development remains poorly resolved. This review synthesizes current knowledge on the functions and regulation of major HSP families (HSP100, HSP90, HSP70, HSP60, and small HSPs) in fish and shellfish larvae and develops mechanistic frameworks linking live feed characteristics to HSP‐mediated stress physiology. Drawing on evidence from Artemia and other crustacean and fish models, we propose a Live Feed–Proteotoxic Stress–HSP (LFP–HSP) axis that integrates feed digestibility, metabolic and oxidative load, and feed‐associated microbiota as key drivers of HSP induction and innate immune function. We further describe ROS–HSP–innate immunity crosstalk and introduce the concept of HSP‐conditioned resilience, whereby controlled, diet‐mediated HSP induction enhances larval tolerance to subsequent husbandry stressors and pathogen challenge. Comparative analysis of commonly used live feeds, including Artemia, rotifers, Moina, Daphnia, and copepods, indicates that differences in nutrient composition, structural complexity, and microbial associations generate distinct HSP expression profiles and stress phenotypes in consuming larvae. Finally, we discuss the application of HSP‐based biomarkers for live feed evaluation, larval quality assessment, and the development of feeding strategies that minimize chronic cellular stress while maximizing robustness in hatchery production of fish and shrimp.