Fig. 8.

Simplified schematic model of polarized growth via microtubule-dependent coordination of local and global Cdc42 GEF activities. (A) In wild-type cells, five main features of the model lead to normal polarized growth: (1) Scd1 (orange) is a plasma membrane-associated ‘local’ Cdc42 GEF at cell tips and maintains a focused polarity zone via positive feedback; (2) Gef1 (pink) is a cytosolic, ‘global’ Gdc42 GEF; (3) microtubules (MTs; green) target the Tea1–Tea4–Pom1 axis (green) to cell tips; (4) this restricts Cdc42 GAP Rga4 (blue) to the plasma membrane at cell sides; (5) Rga4 on the membrane locally counters cytosolic Gef1 activity, preventing net GEF activity at cell sides (different-sized red arrows). (B) The model as applied to scd1Δ and scd1Δ rga4Δ cells. In scd1Δ cells, there is no strong focused polarity zone, but Rga4 can still locally counter global Gef1 activity, leading to greater ‘net’ Gef1 activity in the region of the cell tips, as in wild-type cells. Cells are therefore polarized but wider than wild-type. In scd1Δ rga4Δ cells, absence of Rga4 means that Gef1 is not locally countered anywhere and thus can promote PORTLI growth. Distribution of MTs and Tea1/Tea4/Pom1 will also be abnormal, owing to round cell shape. (C) The model as applied to the genotypes indicated. In scd1^low cells, only a very limited amount of local Cdc42 GEF Scd1 is present at cell tips, and thus the polarity zone is not focused as in wild-type. However, ‘net’ Gef1 activity remains greater in the region of cell tips, and Gef1 cooperates with Scd1. In scd1^low tea1Δ/tea4Δ/pom1Δ cells, Rga4 is no longer spatially restricted, and therefore ‘net’ Gef1 activity is not spatially controlled. This competes with (low) Scd1 and overwhelms its contribution to polarized growth. In scd1^low tea1Δ/tea4Δ/pom1Δ gef1Δ cells, competition from Gef1 is alleviated, allowing the low Scd1 to support polarized growth.