Journal Article

Coordinated regulation of bidirectional COPI transport at the Golgi by CDC42

Soberman, Roy J., Park, Seung-Yeol, Hsu, Victor W., Yang, Jia-Shu, Schmider, Angela B.

2015

Overview

The COPI complex, which has a role in retrograde transport through the Golgi, is shown to also mediate anterograde tubular transport through the Golgi; in response to external stimuli, the small GTPase CDC42 acts as an essential modulator of bidirectional Golgi transport, and promotes the sorting of cargoes destined for anterograde transport into the tubules at the expense of those targeted for retrograde transport. Two-way traffic through Golgi complex tubules The Golgi complex consists of a series of plate-like stacks, connected by structures called tubules. It has been called the cell's 'post office', given its central role in the sorting and distribution of proteins to their proper intracellular destination. Here Victor Hsu and colleagues provide evidence that Golgi tubules play a role in anterograde transport from Golgi towards plasma membrane — a process previously thought to be mediated primarily by the Golgi stacks. They find that the COPI protein complex, known to play a part in retrograde transport through the Golgi, also mediates anterograde tubular transport. This raises the question of how COPI can sort cargoes for transport in opposite directions. The authors find that in response to external stimuli, the small GTPase CDC42 is an essential modulator of bidirectional Golgi transport, promoting the sorting of cargoes destined for anterograde transport into the tubules at the expense of those targeted for retrograde transport. The Golgi complex has a central role in the intracellular sorting of secretory proteins 1 , 2 . Anterograde transport through the Golgi has been explained by the movement of Golgi cisternae, known as cisternal maturation 3 , 4 , 5 . Because this explanation is now appreciated to be incomplete 6 , interest has developed in understanding tubules that connect the Golgi cisternae 7 , 8 , 9 . Here we show that the coat protein I (COPI) complex sorts anterograde cargoes into these tubules in human cells. Moreover, the small GTPase CDC42 regulates bidirectional Golgi transport by targeting the dual functions of COPI in cargo sorting and carrier formation. CDC42 also directly imparts membrane curvature to promote COPI tubule formation. Our findings further reveal that COPI tubular transport complements cisternal maturation in explaining how anterograde Golgi transport is achieved, and that bidirectional COPI transport is modulated by environmental cues through CDC42.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 14 / 631/80/313/1525 / 82 / 96 / Biological transport / cdc42 GTP-Binding Protein - metabolism / Cell Membrane - chemistry / Cell Membrane - metabolism / Cellular biology / Clathrin-coated vesicles / Coat Protein Complex I - metabolism / Coatomer Protein - metabolism / Control / Epidermal growth factor / Golgi apparatus / Golgi Apparatus - metabolism / Guanosine triphosphatase / HeLa Cells / Humanities and Social Sciences / Humans / Kinases / letter / Membrane Glycoproteins - metabolism / Membrane Glycoproteins - secretion / multidisciplinary / Physiological aspects / Protein Transport / Proteins / Receptors, LDL - metabolism / Science / Structure / Viral Envelope Proteins - metabolism / Viral Envelope Proteins - secretion