ARFGAP1 plays a central role in coupling COPI cargo sorting with vesicle formation.

Loading...
Thumbnail Image

Date

2005-01-17

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

222
views
192
downloads

Citation Stats

Abstract

Examining how key components of coat protein I (COPI) transport participate in cargo sorting, we find that, instead of ADP ribosylation factor 1 (ARF1), its GTPase-activating protein (GAP) plays a direct role in promoting the binding of cargo proteins by coatomer (the core COPI complex). Activated ARF1 binds selectively to SNARE cargo proteins, with this binding likely to represent at least a mechanism by which activated ARF1 is stabilized on Golgi membrane to propagate its effector functions. We also find that the GAP catalytic activity plays a critical role in the formation of COPI vesicles from Golgi membrane, in contrast to the prevailing view that this activity antagonizes vesicle formation. Together, these findings indicate that GAP plays a central role in coupling cargo sorting and vesicle formation, with implications for simplifying models to describe how these two processes are coupled during COPI transport.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1083/jcb.200404008

Publication Info

Lee, SY, JS Yang, W Hong, RT Premont and VW Hsu (2005). ARFGAP1 plays a central role in coupling COPI cargo sorting with vesicle formation. J Cell Biol, 168(2). pp. 281–290. 10.1083/jcb.200404008 Retrieved from https://hdl.handle.net/10161/10775.

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.

Scholars@Duke

Premont

Richard Thomas Premont

Associate Professor in Medicine

Critical physiological events throughout the body are controlled by extracellular signals from neurotransmitters and hormones acting on cell surface receptors. Receptors transduce these signals to alter intracellular metabolism and cellular responsiveness through heterotrimeric G protein/second messenger pathways or through small GTP-binding protein/protein kinase cascades.

The mechanisms that control the responsiveness of target organ G protein-coupled receptors include receptor phosphorylation and desensitization by G protein-coupled receptor kinases (GRKs). We have created mice lacking each of the three members of the GRK4 subfamily of GRKs (GRK4, GRK5 and GRK6), and are examining the functional effects of this loss of function on the physiology of receptors controlling gastrointestinal, heart, lung, immune and brain functions.

An important open question in the study of cellular regulation is understanding how cells coordinate the activity of multiple receptor pathways into a coherent cellular response. Our recent discovery that large multidomain ARF GTPase-activating proteins (GAPs) of the GIT family can serve as oligomeric scaffolding proteins for numerous signaling molecules and help coordinate heterotrimeric G protein and multiple small GTP-binding protein pathways, suggests that other multidomain ARF GAPs may also function in analogous manner as coordination centers. We are examining the functional roles of GIT proteins and related ARF GAPs in crosstalk among cellular signaling pathways, with particular emphasis on gastrointestinal and behavioral roles using GIT1 and GIT2 knockout mice.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.