Identification and characterization of a new class of trafficking motifs for controlling clathrin-independent internalization and recycling.
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.
Gong
Qiang
Q
Department of Molecular, Cellular, and Developmental Biology and Neuroscience Research Institute, University of California, Santa Barbara, California 93106, USA.
Weide
Michael
M
Huntsman
Christopher
C
Xu
Zhuojin
Z
Jan
Lily Y
LY
Ma
Dzwokai
D
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D002966:Clathrin; D020662:Guanine Nucleotide Exchange Factors; D006367:HeLa Cells; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics
D000089982:ADP-Ribosylation Factor 6; D002966:Clathrin; D020662:Guanine Nucleotide Exchange Factors; D009419:Nerve Tissue Proteins; C109970:PSD protein, human; D015221:Potassium Channels; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human