Cdc42 regulates microtubule-dependent golgi positioning

Abstract

The molecular mechanisms underlying cytoskeletondependent Golgi positioning are poorly understood. In mammalian cells, the Golgi apparatus is localized near the juxtanuclear centrosome via dynein-mediated motility along microtubules. Previous studies implicate Cdc42 in regulating dynein-dependent motility. Here we show that reduced expression of the Cdc42-specific GTPaseactivating protein, ARHGAP21, inhibits the ability of dispersed Golgi membranes to reposition at the centrosome following nocodazole treatment and washout. Cdc42 regulation of Golgi positioning appears to involve ARF1 and a binding interaction with the vesicle-coat protein coatomer. We tested whether Cdc42 directly affects motility, as opposed to the formation of a trafficking intermediate, using a Golgi capture and motility assay in permeabilized cells. Disrupting Cdc42 activation or the coatomer/Cdc42 binding interaction stimulated Golgi motility. The coatomer/Cdc42-sensitive motility was blocked by the addition of an inhibitory dynein antibody. Together, our results reveal that dynein and microtubuledependent Golgi positioning is regulated by ARF1-, coatomer-, and ARHGAP21-dependent Cdc42 signaling.