Transient Membrane Localization of SPV-1 Drives Cyclical Actomyosin Contractions in the C. elegans Spermatheca

Abstract

Our results demonstrate how transient membrane localization of a novel F-BAR domain, likely via specific binding to curved membranes, coupled to a RhoGAP domain, can provide feedback between a mechanical signal (membrane stretching) and actomyosin contractility. We anticipate this to be a widely utilized feedback mechanism used to balance actomyosin forces in the face of externally applied forces, as well as intrinsic processes involving cell deformation, from single-cell migration to tissue morphogenesis.

Stretch-induced actomyosin contraction in epithelial tubes: Mechanotransduction pathways for tubular homeostasis

“…We recently identified a RhoGAP protein, SPV-1, that regulates contractility of the C. elegans spermatheca [75]. Contraction of the spermatheca is driven by calcium-calmodulin activation of myosin light chain kinase and RHO-1 activation of Rho kinase (ROCK), which leads to the phosphorylation and activation of non-muscle myosin II [63,76].…”

“…In a relaxed membrane state, SPV-1 binds to the membrane through its F-BAR domain and effectively prevents spermatheca contractility by inhibiting RhoA activity through its GAP domain. Upon membrane stretch (oocyte entry into spermatheca), SPV-1 dissociates from the membrane, with subsequent recruitment of active RhoA that induces contractility of the spermatheca [75]. …”

Membrane Supply and Demand Regulates F-Actin in a Cell Surface Reservoir

“…Conversely, to prevent plasma membrane rupture during mechanical stretching in human myotubes and endothelial cells, reservoirs of surface invaginations flatten out (Cheng et al, 2015; Sinha et al, 2011). Membrane is transferred to and from reservoirs as cells change their shape in cytokinesis, cell spreading, phagocytosis, and tissue morphogenesis (Figard et al, 2013; Gauthier et al, 2011; Masters et al, 2013; Sedzinski et al, 2011; Tan and Zaidel-Bar, 2015). Thus, the sheer number and diversity of biological processes in which reservoirs participate argue that they represent a fundamental mechanism used by cells to control surface area.…”

Mechanotransduction: Feeling the Squeeze in the C. elegans Reproductive System

“…As is the case for other tubes of cells [9], Tan and Zaidel-Bar [6] show that the spermatheca is stimulated to contract by the activation of the small GTPase Rho. Rho is a switch-like protein that is converted to the GTP-bound ‘on’ state by guanine nucleotide exchange factors (RhoGEFs), and switched ‘off’ by GTPase-activating proteins (RhoGAPs), which stimulate the hydrolysis of GTP to GDP [10].…”

“…A critical barrier to progress in this field is the need for intact systems that will enable the study of mechanotransduction in living animals. A new study, published in this issue of Current Biology , now helps to establish the Caenorhabditis elegans spermatheca as an in vivo model system for the study of how cells coordinate tissue-level responses to mechanical input, and identifies a novel RhoGAP, SPV-1, which can directly detect changes in membrane topology [6]. …”