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Exp Cell Res. 2017 Dec 15;361(2):265-276. doi: 10.1016/j.yexcr.2017.10.026. Epub 2017 Oct 26.

VANGL2 interacts with integrin αv to regulate matrix metalloproteinase activity and cell adhesion to the extracellular matrix.

Author information

1
Department of Biology, Middle Tennessee State University, 1301 East Main Street, Murfreesboro, TN 37132, USA.
2
Department of Biology, Middle Tennessee State University, 1301 East Main Street, Murfreesboro, TN 37132, USA. Electronic address: jason.jessen@mtsu.edu.

Abstract

Planar cell polarity (PCP) proteins are implicated in a variety of morphogenetic processes including embryonic cell migration and potentially cancer progression. During zebrafish gastrulation, the transmembrane protein Vang-like 2 (VANGL2) is required for PCP and directed cell migration. These cell behaviors occur in the context of a fibrillar extracellular matrix (ECM). While it is thought that interactions with the ECM regulate cell migration, it is unclear how PCP proteins such as VANGL2 influence these events. Using an in vitro cell culture model system, we previously showed that human VANGL2 negatively regulates membrane type-1 matrix metalloproteinase (MMP14) and activation of secreted matrix metalloproteinase 2 (MMP2). Here, we investigated the functional relationship between VANGL2, integrin αvβ3, and MMP2 activation. We provide evidence that VANGL2 regulates cell surface integrin αvβ3 expression and adhesion to fibronectin, laminin, and vitronectin. Inhibition of MMP14/MMP2 activity suppressed the cell adhesion defect in VANGL2 knockdown cells. Furthermore, our data show that MMP14 and integrin αv are required for increased proteolysis by VANGL2 knockdown cells. Lastly, we have identified integrin αvβ3 as a novel VANGL2 binding partner. Together, these findings begin to dissect the molecular underpinnings of how VANGL2 regulates MMP activity and cell adhesion to the ECM.

KEYWORDS:

Adhesion; Extracellular matrix; Integrins; MMP14; MMP2; VANGL2

PMID:
29097183
PMCID:
PMC5701855
DOI:
10.1016/j.yexcr.2017.10.026
[Indexed for MEDLINE]
Free PMC Article

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