Premium
The novel role of the matricellular protein Cyr61 in bridging LPA and integrin signaling pathways leading to cell migration
Author(s) -
Cui MeiZhen,
Wu Daniel Dongwei,
Zhang Fuqiang,
Hao Feng,
Xu Xuemin
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.604.10
Subject(s) - cyr61 , matricellular protein , microbiology and biotechnology , cell migration , focal adhesion , integrin , lysophosphatidic acid , ctgf , signal transduction , gene knockdown , extracellular matrix , biology , cell , chemistry , receptor , cell culture , growth factor , biochemistry , genetics
Lysophosphatidic acid (LPA), a potent bioactive lipid, markedly induces smooth muscle cell (SMC) migration. We identified a novel function of the de novo synthesized matricellular protein Cyr61, which bridges LPA and integrin signaling pathways leading to cell migration. LPA transiently and markedly induced Cyr61 mRNA expression and the temporal and spatial expression of Cyr61 proteins in SMCs. The de novo synthesized Cyr61 proteins promptly accumulate in the Golgi apparatus and then translocate to the extracellular matrix. Using primary SMCs from LPA receptor knockout mice, we identified that LPA1 receptor is required for LPA‐induced Cyr61 expression. Neutralization or knockdown of Cyr61 protein expression blocked LPA‐induced cell migration, indicating the novel regulatory role of the induced matricellular protein Cyr61 in LPA‐induced cell migration. LPA induces the activation of intracellular focal adhesion kinase (FAK) in SMCs. Interestingly, 1) knockdown of Cyr61 blocked LPA‐induced cellular FAK activation and cell migration, and 2) knockdown of the expression of integrins alpha6, beta1 and beta3 prevented LPA or Cyr61‐induced FAK activation and cell migration. These data reveal for the first time that a novel LPA/Cyr61 pathway controls cell migration and that the matricellular protein Cyr61 bridges LPA signaling and integrin signaling, which, in turn, activates FAK leading to cell migration.