How Diffusion Impacts Cortical Protein Distribution in Yeasts

Abstract

Proteins associated with the yeast plasma membrane often accumulate asymmetrically within the plane of the membrane. Asymmetric accumulation is thought to underlie diverse processes, including polarized growth, stress sensing, and aging. Here, we review our evolving understanding of how cells achieve asymmetric distributions of membrane proteins despite the anticipated dissipative effects of diffusion, and highlight recent findings suggesting that differential diffusion is exploited to create, rather than dissipate, asymmetry. We also highlight open questions about diffusion in yeast plasma membranes that remain unsolved.

Keywords: Cdc42; cell polarity; diffusion.

Figure 1

Stereotyped pattern of secretion enables localization dependent on the time of synthesis during the cell cycle. (A) Arrows indicate secretion patterns through the cell cycle. (B) With no diffusion, cell wall-linked proteins are spatially distributed in a manner that reflects where they were initially secreted. This leads to their accumulation in the mother, the bud, or at sites of cytokinesis, depending on the timing of their synthesis during the cell cycle.

Figure 2

Dynamic localization of integral membrane and peripheral membrane proteins. (A) Asymmetric distribution of v-SNAREs arises from vesicle-mediated delivery of v-SNAREs to polarity sites (left), slow diffusion of v-SNAREs on the membrane (middle), and recycling via endocytosis (right). Note that while these processes are highlighted in separate panels for clarity, they all occur continuously. (B) Cdc42 localization through the cell cycle. (C) Asymmetric distribution of GTP-Cdc42 arises from deposition of GDP-Cdc42 on the membrane by GDI followed by local activation by GEF (left), diffusion of GTP-Cdc42 on the membrane (middle), and inactivation by GAP allowing GDI to pluck GDP-Cdc42 off the membrane, recycling it to the cytoplasm (right). Note that while these processes are highlighted in separate panels for clarity, they all occur continuously. Recruitment of GEF to sites with GTP-Cdc42 enables a positive feedback loop that loads GTP on neighboring Cdc42.

Figure 3

Differential diffusion of Cdc42. (A) Location-dependent differential diffusion: zones of fast and slow mobility (blue and orange, respectively) would cause a protein (green) to become concentrated in the slow-diffusion zone. (B) GFP-Cdc42 displays patchy localization at polarity sites. (C) Patchy localization could be explained by alternating zones of slow and fast mobility. (D) Patchy localization of GFP-Cdc42 could also be explained by exclusion of GFP-Cdc42 from endocytic sites (clathrin-coated pits). (E) Differential diffusion of GTP-Cdc42 and GDP-Cdc42. Localized GEF activity (blue) and uniform GAP activity (orange) would lead to local activation of Cdc42 in the GEF zone. If GTP-Cdc42 (green) diffuses less than GDP-Cdc42 (red), then Cdc42 accumulates in the GEF zone. Arrows indicate high mobility of GDP-Cdc42 relative to GTP-Cdc42.