Parallel Actin-Independent Recycling Pathways Polarize Cdc42 in Budding Yeast.
Abstract
The highly conserved Rho-family GTPase Cdc42 is an essential regulator of polarity
in many different cell types. During polarity establishment, Cdc42 becomes concentrated
at a cortical site, where it interacts with downstream effectors to orient the cytoskeleton
along the front-back axis. To concentrate Cdc42, loss of Cdc42 by diffusion must be
balanced by recycling to the front. In Saccharomyces cerevisiae, the guanine nucleotide
dissociation inhibitor (GDI) Rdi1 recycles Cdc42 through the cytoplasm. Loss of Rdi1
slowed but did not eliminate Cdc42 accumulation at the front, suggesting the existence
of other recycling pathways. One proposed pathway involves actin-directed trafficking
of vesicles carrying Cdc42 to the front. However, we found no role for F-actin in
Cdc42 concentration, even in rdi1Δ cells. Instead, Cdc42 was still able to exchange
between the membrane and cytoplasm in rdi1Δ cells, albeit at a reduced rate. Membrane-cytoplasm
exchange of GDP-Cdc42 was faster than that of GTP-Cdc42, and computational modeling
indicated that such exchange would suffice to promote polarization. We also uncovered
a novel role for the Cdc42-directed GTPase-activating protein (GAP) Bem2 in Cdc42
polarization. Bem2 was known to act in series with Rdi1 to promote recycling of Cdc42,
but we found that rdi1Δ bem2Δ mutants were synthetically lethal, suggesting that they
also act in parallel. We suggest that GAP activity cooperates with the GDI to counteract
the dissipative effect of a previously unappreciated pathway whereby GTP-Cdc42 escapes
from the polarity site through the cytoplasm.
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https://hdl.handle.net/10161/13035Published Version (Please cite this version)
10.1016/j.cub.2016.06.047Publication Info
Woods, Benjamin; Lai, Helen; Wu, Chi-Fang; Zyla, Trevin R; Savage, Natasha S; & Lew,
Daniel J (2016). Parallel Actin-Independent Recycling Pathways Polarize Cdc42 in Budding Yeast. Curr Biol, 26(16). pp. 2114-2126. 10.1016/j.cub.2016.06.047. Retrieved from https://hdl.handle.net/10161/13035.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Daniel Julio Lew
James B. Duke Distinguished Professor of Pharmacology and Cancer Biology
Our research interests focus on the control of cell polarity. Cell polarity is a
nearly universal feature of eukaryotic cells. A polarized cell usually has a single,
clear axis of asymmetry: a “front” and a “back”. In the past
several years it has become apparent that the highly conserved Rho-family GTPase Cdc42,
first discovered in yeast, is a component of a master pathway, employed time and again
to promote polarity in different contexts.
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.

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