PubMed 25344254

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClIC4

Title: CLIC4 regulates cell adhesion and β1 integrin trafficking.

Authors: Elisabetta Argenzio, Coert Margadant, Daniela Leyton-Puig, Hans Janssen, Kees Jalink, Arnoud Sonnenberg, Wouter H Moolenaar

Journal, date & volume: J. Cell. Sci., 2014 Dec 15 , 127, 5189-203

PubMed link:

Chloride intracellular channel protein 4 (CLIC4) exists in both soluble and membrane-associated forms, and is implicated in diverse cellular processes, ranging from ion channel formation to intracellular membrane remodeling. CLIC4 is rapidly recruited to the plasma membrane by lysophosphatidic acid (LPA) and serum, suggesting a possible role for CLIC4 in exocytic-endocytic trafficking. However, the function and subcellular target(s) of CLIC4 remain elusive. Here, we show that in HeLa and MDA-MB-231 cells, CLIC4 knockdown decreases cell-matrix adhesion, cell spreading and integrin signaling, whereas it increases cell motility. LPA stimulates the recruitment of CLIC4 to β1 integrin at the plasma membrane and in Rab35-positive endosomes. CLIC4 is required for both the internalization and the serum- or LPA-induced recycling of β1 integrin, but not for EGF receptor trafficking. Furthermore, we show that CLIC4 suppresses Rab35 activity and antagonizes Rab35-dependent regulation of β1 integrin trafficking. Our results define CLIC4 as a regulator of Rab35 activity and serum- and LPA-dependent integrin trafficking.