Cdc42 plays a key role in yeast cell polarization

1. Cdc42 plays a key role in yeast cell polarization Chao Wang June 17, 2005

2. Cell division • Polarization • Small GTPases • Cdc42 SGD Description:Small rho-like GTPase, essential for establishment and maintenance of cell polarity; mutants have defects in the organization of actin and septins

3. Cdc42, a small GTPaseof the Rho family, stands out as playing a central role inestablishing cell polarity in all eukaryotic cells, irrespective ofthe biological context. • Two fundamental questions: • How can a diverse set ofpolarization signals regulate Cdc42 ? • How can this smallmolecule control the multiple cellular activities required forcell polarization ?

4. Outline • Cell polarization requires Cdc42 activity • Spatial and temporal control of Cdc42p activity • Cdc42p activates multiple polarity pathways

6. Cell polarization requires Cdc42 activity • In the absence of Cdc42p, cellgrowth is no longer polarized but instead gives rise to large,round, unbudded cells. • A GTP-bound state and a GDP-bound state. Cdc42-GTP levels can be regulated either positively byguanine nucleotide exchange factors (GEFs) or negatively byGTPase-activating proteins (GAPs). • In yeast, Cdc24p is the major GEFcontrolling Cdc42p activity and cell polarization

7. Three importantconclusions • Cdc42p activation is both necessary andsufficient to promote spontaneous cell polarization • Cdc42pactivation must be restricted temporally and spatially • Inphysiological conditions, Cdc42p function requires its abilityto hydrolyse GTP

8. Spatial and temporal control of Cdc42pactivity • The local activation ofCdc42p at the presumptive growth site • The spatial control of Cdc42p activity isalsoachievedby recruitment of Cdc42pitself to the site of polarized growth • Mathematical simulations suggest that the local concentrationof Cdc42p is generated by a stochastic increase of activatedCdc42p on plasma membrane sites and is amplified by apositive feedback loop

9. Cdc42p activates multiple polarity pathways Polarized cell growth is a complex processthat requires the coordinationof multiple cellular activities, including polarizationof the actin and microtubule cytoskeletons and directed vesicletrafficking to deliver cell wall and plasma membranecomponents to the bud site

10. Cdc42p directly promotes the selforganizationof septins, leading to the formation of a ring thatdemarcates the mother and the bud • Actinstructures accumulate at the bud site and, in budding yeast,these are responsible for most of the subsequent eventsassociated with cell polarization • Cdc42p not onlyregulates actin organization, but also directly regulatesexocytosis. Polarization of the actin cytoskeleton also contributes totransport of cytoplasmic microtubules to the bud

11. Some general principles • The localizedactivation of Cdc42, induced through various intrinsic orextrinsic signals • The activation of multiple Cdc42 targetproteins, leading to the co-ordinated regulation of cellfunctions • The use of feedback loops involving Cdc42effectors that tighten the spatial and temporal regulation of thepolarization machinery.

12. The End