Kim, B.-s. | Search bioRxiv

bioRxiv2026

The galectin-3 carbohydrate recognition domain maintains plasma membrane phosphatidylserine required for KRAS function

KRAS is a small GTPase essential for cellular proliferation, differentiation, and survival. It is predominantly localized to the plasma membrane (PM), where it forms nanoclusters essential for signal transduction. This PM binding and nanoclustering strictly depend on phosphatidylserine (PtdSer), an anionic phospholipid enriched in the inner PM leaflet. Galectin-3 (Gal-3), a {beta}-galactoside-binding lectin implicated in cell growth, migration and tumor progression, has been shown to regulate KRAS PM binding and nanoclustering. Here, we demonstrate that Gal-3 knockout (KO) or inhibition of its carbohydrate recognition domain (CRD) depletes KRAS and PtdSer from the PM. Exogenous PtdSer supplementation fully restores PM PtdSer and partially restores KRAS PM binding, indicating that Gal-3 promotes KRAS PM binding in part by maintaining PM PtdSer content. Total cellular PtdSer, PM PI4P, cholesterol and GM3 are unchanged, excluding these established regulators of PM PtdSer. Instead, Gal-3 CRD inhibition disrupts the cellular balance of sphingomyelin (SM) and ceramide, alters intracellular SM distribution, and impairs the endocytic and recycling transport of PtdSer, SM, and epidermal growth factor receptor (EGFR). Together, our findings demonstrate that Gal-3 CRD activity sustains PM PtdSer content through endocytic trafficking, providing the PM lipid composition required for KRAS PM spatial organization.

cell biology↗

bioRxiv2026

Microgravity affects the nervous system and aging in C. elegans through reduced tactile stimulation

Space travel is becoming accessible, yet our understanding of how space environment and microgravity ({micro}G) affect biology, physiology, and health remains incomplete. We investigated {micro}G effects on neuromuscular development and aging in Caenorhabditis elegans. Nematodes in {micro}G showed downregulation of genes related to synaptic signaling, dopamine response, locomotion, and cuticle development, with impaired synaptic vesicle dynamics, reduced motility, and shorter body lengths. Aged worms in {micro}G showed decreased collagen gene expression, increased motor neuron defects, synaptic vesicle accumulation and decreased release, and mitochondrial morphology collapse in body wall muscles, indicating accelerated aging. MEC-4 mechanoreceptor was identified as a key mediator of {micro}G-induced body length reduction and changes in extracellular matrix gene expression. {micro}G conditions suppressed mechanoreceptor genes, suggesting multiple mechanosensory systems are affected. Physical stimulation through culture medium with small beads in space mitigated many {micro}G-induced expression changes, including mechanoreceptors, neuromuscular defects, and aging-related phenotypes. These results highlight mechanical stimulis role in maintaining neuromuscular integrity during spaceflight and suggest restoring tactile input could counter health risks from reduced stimulation in long-term space missions. SIGNIFICACEWe found that microgravity ({micro}G) conditions suppress the expression of multiple mechanoreceptor genes in Caenorhabditis elegans, indicating that several mechanosensory systems are affected during spaceflight. Importantly, reintroducing physical stimulation by adding small beads to the culture medium in space partially reversed many of these {micro}G-induced gene expression changes. This intervention also mitigated neuromuscular defects and aging-related phenotypes observed under {micro}G conditions. Collectively, these findings underscore the essential role of mechanical stimuli in preserving neuromuscular integrity during space missions and suggest that restoring tactile input may be a promising strategy to counteract the health risks associated with reduced tactile stimulation during prolonged spaceflights.

systems biology↗