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Analyses of Actin Dynamics, Clutch Coupling and Traction Force for Growth Cone Advance

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Cdc42 GTPase dynamics control directional growth responses.

Alexandra C Brand¹, Emma Morrison, Stephen Milne

¹School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America

|January 4, 2014

Summary

Calcium influx amplifies Cdc42-mediated directional growth in Candida albicans by enhancing Cdc42 apical trafficking. This process is crucial for polarity establishment, particularly in response to environmental cues.

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Area of Science:

Cell biology
Mycology
Biochemistry

Background:

Polarized cell growth is vital for cellular function and development.
In Candida albicans, Cdc42 (a Rho-family GTPase) regulates hyphal growth, and calcium (Ca2+) influx is necessary for tropic responses.
The precise regulatory connection between Ca2+ influx and Cdc42 dynamics in directed growth remains largely undefined.

Purpose of the Study:

To investigate the interplay between Ca2+ influx and Cdc42 polarity-complex dynamics.
To elucidate the role of Ca2+ in regulating Cdc42-dependent hyphal growth responses.
To understand the mechanisms by which environmental cues influence cell polarity.

Main Methods:

Utilized galvanotropic and thigmotropic responses in Candida albicans as model systems for studying directed hyphal growth.
Employed gene deletion strategies targeting key regulators of Cdc42, including Rdi1 (guanine nucleotide dissociation inhibitor) and Bnr1 (formin).
Investigated the effects of disrupting Cdc42 GTPase activating proteins (Rga2, Bem3) and manipulating Cdc42 activity (GTP-locked mutant).

Main Results:

Disruption of Cdc42 recycling pathways (Rdi1, Bnr1 deletion) abolished cathodal polarization, which was restored by extracellular Ca2+.
Loss of Cdc42 GTPase activating proteins (Rga2, Bem3) also eliminated cathodal polarization, but this effect was not rescued by Ca2+.
GTP-locked Cdc42 reversed hyphal polarity from cathodal to anodal, an effect enhanced by Ca2+, indicating Cdc42 GTP hydrolysis is required for directional cues.

Conclusions:

Ca2+ influx acts as a crucial amplifier of Cdc42-mediated directional growth signals, partly by promoting Cdc42 apical trafficking.
The Cdc42 GTP hydrolysis cycle is essential for responding to directional cues like electric fields.
The Ca2+-binding EF-hand motif in Cdc24 (Cdc42 activator) is vital for polarity establishment in yeast but not for polarity maintenance in established hyphae.