Activation of the Small G Protein Arf6 by Dynamin2 Through Guanine Nucleotide Exchange Factors in Endocytosis

Overview

Journal Sci Rep

Specialty Science

Date 2015 Oct 28

PMID 26503427

Citations 8

Authors

Risa Okada

Yohei Yamauchi

Tsunaki Hongu

Yuji Funakoshi

Norihiko Ohbayashi

Hiroshi Hasegawa

Yasunori Kanaho

Affiliations

Soon will be listed here.

Abstract

The small G protein Arf6 and the GTPase dynamin2 (Dyn2) play key roles in clathrin-mediated endocytosis (CME). However, their functional relationship remains obscure. Here, we show that Arf6 functions as a downstream molecule of Dyn2 in CME. Wild type of Dyn2 overexpressed in HeLa cells markedly activates Arf6, while a GTPase-lacking Dyn2 mutant does not. Of the Arf6-specific guanine nucleotide exchange factors, EFA6A, EFA6B, and EFA6D specifically interact with Dyn2. Furthermore, overexpression of dominant negative mutants or knockdown of EFA6B and EFA6D significantly inhibit Dyn2-induced Arf6 activation. Finally, overexpression of the binding region peptide of EFA6B for Dyn2 or knockdown of EFA6B and EFA6D significantly suppresses clathrin-mediated transferrin uptake. These results provide evidence for a novel Arf6 activation mechanism by Dyn2 through EFA6B and EFA6D in CME in a manner dependent upon the GTPase activity of Dyn2.

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