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Cdc42 regulates microtubule-dependent Golgi positioning.
Heidi Hehnly1, Weidong Xu, Ji-Long Chen
1Department of Molecular Physiology & Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Traffic (Copenhagen, Denmark)
|June 8, 2010
Summary
The study reveals how ARHGAP21 regulates Golgi positioning by controlling Cdc42 signaling, impacting dynein-mediated cell transport. This finding clarifies cytoskeleton-dependent Golgi apparatus localization mechanisms.
Area of Science:
- Cell Biology
- Molecular Mechanisms
- Cytoskeleton Dynamics
Background:
- The Golgi apparatus localization near the centrosome in mammalian cells relies on dynein-mediated microtubule transport.
- Cdc42 has been implicated in regulating this dynein-dependent motility, but the precise mechanisms are unclear.
Purpose of the Study:
- To elucidate the molecular mechanisms of cytoskeleton-dependent Golgi positioning.
- To investigate the role of ARHGAP21 and Cdc42 in regulating Golgi apparatus localization.
Main Methods:
- Utilized reduced expression of ARHGAP21 to observe effects on Golgi repositioning after nocodazole treatment.
- Employed a Golgi capture and motility assay in permeabilized cells to assess Cdc42's direct impact on motility.
- Investigated the involvement of ARF1 and coatomer in Cdc42-mediated Golgi positioning.
Main Results:
- Reduced ARHGAP21 expression impaired Golgi repositioning to the centrosome.
- Cdc42 regulation of Golgi positioning involves ARF1 and coatomer binding.
- Disrupting Cdc42 activation or coatomer/Cdc42 interaction enhanced Golgi motility.
- This motility was dynein-dependent and blocked by an inhibitory dynein antibody.
Conclusions:
- Dynein and microtubule-dependent Golgi positioning is regulated by a signaling pathway involving ARF1, coatomer, and ARHGAP21-dependent Cdc42.
- ARHGAP21 acts as a Cdc42-specific GTPase-activating protein influencing Golgi apparatus localization.
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