Actin-Based Transport Adapts Polarity Domain Size to Local Cellular Curvature

Abstract

Intracellular structures and organelles such as the nucleus, the centrosome, or the mitotic spindle typically scale their size to cell size [1]. Similarly, cortical polarity domains built around the active form of conserved Rho-GTPases, such as Cdc42p, exhibit widths that may range over two orders of magnitudes in cells with different sizes and shapes [2-6]. The establishment of such domains typically involves positive feedback loops based on reaction-diffusion and/or actin-mediated vesicle transport [3, 7, 8]. How these elements may adapt polarity domain size to cellular geometry is not known. Here, by tracking the width of successive oscillating Cdc42-GTP domains in fission yeast spores [9], we find that domain width scales with local cell-surface radii of curvature over an 8-fold range, independently of absolute cell volume, surface, or Cdc42-GTP concentration. This local scaling requires formin-nucleated cortical actin cables and the fusion of secretory vesicles transported along these cables with the membrane. These data suggest that reaction-diffusion may set a minimal domain size and that secretory vesicle transport along actin cables may dilute and extend polarity domains to adapt their size to local cell-surface curvature. This work reveals that actin networks may act as micrometric curvature sensors and uncovers a generic morphogenetic principle for how polarity domains define their size according to cell morphologies.

Cell Polarity in Yeast

“…A recent study on germinating spores of S. pombe suggested that the size of a Cdc42 cluster depends primarily on the micrometer-scale curvature of the membrane (Figure 7 d ) (Bonazzi et al 2015). In this system, Cdc42 clusters migrated around the cell before stabilizing to promote polarized growth (Bonazzi et al 2014).…”

“…Moreover, during cell outgrowth, Cdc42 clusters shrank to accommodate the increased curvature (Figure 7 d ). These findings suggest that the initial outgrowth zone is determined by mechanical criteria reflecting the biophysics of the cell wall, with the Cdc42 cluster size adjusting in response to the local cell shape (Bonazzi et al 2015). …”

“…Curvature scaling was dependent on actin and exocytosis, leading to a model in which dilution of polarity factors by vesicle fusion regulates the size of a polarity cluster (Bonazzi et al 2015). According to this hypothesis, cell curvature affects the catchment area from which actin cables can recruit secretory vesicles: Flatter regions enable more vesicle recruitment, diluting and hence broadening the polarity site.…”

Systematic Mapping of cell Wall Mechanics in the Regulation of Cell Morphogenesis

“…As another independent mean to dynamically alter diameter, we used microfabricated PDMS channels. We grew large rga4Δ mutant cells into narrow microchannels forcing them to adapt a smaller wild-type like diameter (28,29). Remarkably, at the channels exit, cells popped out and recovered their normal large diameters in time-scales of few minutes without growing new CW ( Fig.S4G-S4I).…”

Mechanosensation Dynamically Coordinates Polar Growth and Cell Wall Assembly to Promote Cell Survival

“…This is because growth is an integrated output of multiple intertwined biochemical and biomechanical elements which dynamically probe and alter the cell surface to accommodate surface expansion. Those may include surface material synthesis mediated by processes such as exocytosis and endocytosis (Hepler et al, 2001;Novick and Schekman, 1979), as well as osmotic forces and mechanical elements which set the elasticity of the cell surface, like the actin cortex, the glycocalyx or the CW (Davi and Minc, 2015;Huang and Ingber, 1999;Salbreux et al, 2012). How those modules which act at various time and length scales may dynamically feedback onto each other to control the rate of cell surface expansion remain an outstanding open question.…”