Biology subjects

Helenius, J.

Publications and source records attributed to Helenius, J..

3 recordsLinked to original sources

bioRxiv2025

Load-dependent RGD-context sensing via αV-class integrins reprograms cellular adhesion and mechanics within seconds

The cellular ability to biophysically and biochemically recognize extracellular matrix proteins is fundamental to adhesion, mechanics, migration, and morphogenesis, and influences homeostasis and disease. However, the mechanisms underlying integrin-mediated mechanosensing of the arginine-glycine-aspartic acid (RGD)-motif of vitronectin and fibronectin remain elusive. Here, we discover that within seconds of sensing vitronectin, V-class integrins initiate and strengthen adhesion biphasically through complementary mechanotransduction pathways, which rely on the catch bond behavior of single V{beta}3 integrins. The first adhesion phase requires V{beta}3 and V{beta}5 integrin-associated actomyosin and FAK activity, while V{beta}5 integrin additionally requires clathrin-mediated endocytosis. With elevating mechanical load, the second phase requires V{beta}3 integrin-directed Arp2/3, cSrc, and PI3K signaling that dominates V{beta}5 integrin in organizing the consensus adhesome on vitronectin. Simultaneously, V{beta}5 integrin regulates the mechanical stiffening of fibroblasts. Thus, V-class integrins exhibit rapid RGD-motif- and {beta}-subunit-specific programs to synergistically guide mammalian cell adhesion and mechanics upon encountering diverse extracellular environments.

biophysics↗

bioRxiv2022

The CRL4B E3 ligase regulates mitosis by recruiting phospho-specific DCAFs

The cullin-4 paralogs CUL4A and CUL4B assemble E3 ubiquitin ligase complexes regulating multiple chromatin-associated cellular functions. Although they are structurally similar, we found that the unique N-terminal extension of CUL4B is heavily phosphorylated during mitosis, and the phosphorylation pattern is perturbed in the CUL4B-P50L mutation causing X-linked intellectual disability (XLID). Phenotypic characterization and mutational analysis revealed that CUL4B phosphorylation is required for efficient progression through mitosis, controlling spindle positioning and cortical tension. Interestingly, while CUL4B phosphorylation triggers chromatin exclusion, it critically promotes binding to actin regulators and two previously unrecognized, CUL4B-specific DCAFs, LIS1 and WDR1. Indeed, co-immunoprecipitation experiments and biochemical analysis revealed that LIS1 and WDR1 interact with DDB1, but their binding requires the phosphorylated N-terminal domain of CUL4B. Together, our study uncovers previously unrecognized DCAFs relevant for mitosis and brain development that specifically bind CUL4B, but not the CUL4B-P50L patient mutant, by a phosphorylation-dependent mechanism.

cell biology↗

bioRxiv2018

Spatiotemporally controlled Myosin relocalization and internal pressure cause biased cortical extension to generate sibling cell size asymmetry

Metazoan cells can generate unequal sized sibling cells during cell division. This form of asymmetric cell division depends on spindle geometry and Myosin distribution but the underlying mechanics are unclear. Here, we use atomic force microscopy and live cell imaging to elucidate the biophysical forces involved in the establishment of physical asymmetry in Drosophila neural stem cells. We show that the force driving initial apical membrane expansion is provided by hydrostatic pressure, peaking shortly after anaphase onset, and enabled by a relieve of actomyosin contractile tension on the apical cell cortex. The subsequent increase in contractile forces at the cleavage furrow, combined with the relocalization of basally located Myosin results in basal membrane extension and sustained apical expansion. We propose that spatiotemporally controlled actomyosin contractile tension and hydrostatic pressure enables stereotypic biased membrane expansion to generate sibling cell size asymmetry.

cell biology↗