Identification and Characterization of a New Class of Trafficking Motifs for Controlling Clathrin-independent Internalization and Recycling

Dzwokai Ma,Qiang Gong,Zhuojin Xu,Lily Y. Jan,Michael Weide,Christopher Huntsman

doi:10.1074/jbc.m700767200

Abstract

Plasma membrane proteins such as receptors and ion channels allow a cell to communicate with its environment and regulate many intracellular activities. Thus, the proper control of the surface number of these proteins is essential for maintaining the structural and functional homeostasis of a cell. Internalization and recycling plays a key role in determining the surface density of receptors and channels. Whereas the clathrin-mediated internalization and its associated recycling have been the focus of research in this field, recent studies have revealed that an increasing number of receptors and channels enter a cell via clathrin-independent pathways. However, little is known about the trafficking motifs involved in controlling clathrin-independent internalization and various associated recycling pathways. By using a potassium channel as a model system, we identified a class of trafficking motifs that function along a clathrin-independent pathway to increase the surface density of a membrane protein by preventing its rapid internalization and/or facilitating its recycling via the ADP-ribosylation factor 6-dependent recycling pathway. Moreover our data suggest that these motifs may enhance the association of membrane proteins with the EFA6 family of guanine nucleotide exchange factors for ADP-ribosylation factor 6.

Highlights

Because internalization and recycling regulate the surface density of receptors and channels, they play crucial roles in the function of these proteins
The clathrin-dependent internalization pathway has been the focus of research in this field because it is mediated by specific trafficking motifs located within cargo proteins and allows a cell to selectively control its surface level of particular receptors and channels
Identification and characterization of these motifs have greatly facilitated our understanding of clathrin-mediated internalization. No such trafficking motifs have been identified for clathrin-independent internalization pathways, and much less is known about these trafficking events

Summary

Introduction

Because internalization and recycling regulate the surface density of receptors and channels, they play crucial roles in the function of these proteins. In cell types such as HeLa and COS-7 cells, the cargo proteins entering the Arf6 recycling pathway are internalized by a clathrin-independent mechanism [12, 14].

Results

Conclusion