bioRxiv Science⌕ Search

Biology subjects

Wolowczyk, A.

Publications and source records attributed to Wolowczyk, A..

2 recordsLinked to original sources

Mechanical forces stimulate Golgi export

Cells face diverse mechanical stimuli that vary with cell type, state, and pathological conditions. Mechanobiology investigates how cells sense and respond to these forces. While most work has focused on the cell surface and nucleus as primary mechanosensors, how intracellular organelles adapt to extracellular mechanical forces remains largely unknown. Here, we show that extracellular mechanical signals influence the secretory function of the Golgi apparatus. By subjecting adherent cells to mechanical challenges -cell spreading on different ligands, altered substrate stiffness, or equibiaxial strain-, we reveal that extracellular forces modulate Golgi-to-cell surface carrier biogenesis, thereby regulating exocytosis. Together with changes in Golgi membrane tension, we identify molecular determinants of the mechanotransduction pathway, including microtubule acetylation, diacylglycerol production, and protein kinase D activity. In turn, inhibition of Golgi export suppresses this mechanoresponse and causes impaired cell spreading. These findings uncover a bidirectional mechanotransduction axis in which extracellular mechanics tune Golgi secretory output, providing a framework for investigating organelle-based mechanoadaptation in physiology and disease.

cell biology↗

Filopodial protrusion driven by density-dependent Ena-TOCA-1 interactions

Filopodia are narrow actin-rich protrusions with important roles in neuronal development. The neuronally-enriched TOCA-1/CIP4 family of F-BAR and SH3 domain adaptor proteins have emerged as upstream regulators that link membrane interactions to actin binding proteins in lamellipodia and filopodia, including WAVE and N-WASP nucleation promoting factors and formins. Here, we demonstrate a direct interaction between TOCA-1 and Ena/VASP actin filament elongators that is mediated by clustered SH3 domain interactions. Using Xenopus retinal ganglion cell axonal growth cones, where Ena/VASP proteins have a native role in filopodia extension, we show that TOCA-1 localises to filopodia and lamellipodia, with a retrograde flow of puncta, and correlates with filopodial protrusion. Two-colour single molecule localization microscopy of TOCA-1 and Ena supports their nanoscale association. TOCA-1 clusters coalesce at advancing lamellipodia and filopodia and operate synergistically with Ena to promote filopodial protrusion dependent on a functional SH3 domain. In analogous yet distinct ways to lamellipodin and IRSp53, we propose that transient TOCA-1 clusters recruit and promote Ena activity to orchestrate filopodial protrusion.

cell biology↗