Force-Control in Neurons via Curved Membrane Nanodomains
Work in our lab is focused on a particular type of receptor-independent signaling platforms, where mechanical forces at the PM are translated into classical biochemical signal transduction cascades via nanoscale membrane deformations. This type of mechano-chemical signal translation at cellular membranes, which relies on recruitment of curvature-sensitive signaling molecules to curved membranes, has been suggested to be involved in a variety of biological processes. However, only recent technical advancements allow to study these processes at the physiological scale. Here we aim to investigate how transiently forming curved PM nanodomains regulate actin-based forces in developing mouse neurons. Using novel image analysis tools we have already identified several curvature-sensitive actin-regulatory proteins that shape neuronal architecture, which now will be further analyzed. Specifically, we aim to investigate the function of the currently uncharacterized curvature-sensitive actin-regulatory protein ArhGEF38 in developing neurons as well as how signaling from Baiap2 and ArhGAP44, two curvature-sensing proteins with opposing impact on actin polymerization dynamics, is integrated at individual membrane nanodomains. Findings from these studies are of general relevance, as spatio-temporal control of actin-based forces via curved membrane nanodomains is ubiquitously present in cells from many tissues and species.