TRPM7 Regulates Cell Adhesion by Controlling the Calcium-dependent Protease Calpain

Li-Ting Su,Maria A Agapito,Mingjiang Li,William T.N Simonson,Anna Huttenlocher,Raymond Habas,Lixia Yue,Loren W Runnels

doi:10.1074/jbc.m512885200

Abstract

m-Calpain is a protease implicated in the control of cell adhesion through focal adhesion disassembly. The mechanism by which the enzyme is spatially and temporally controlled is not well understood, particularly because the dependence of calpain on calcium exceeds the submicromolar concentrations normally observed in cells. Here we show that the channel kinase TRPM7 localizes to peripheral adhesion complexes with m-calpain, where it regulates cell adhesion by controlling the activity of the protease. Our research revealed that overexpression of TRPM7 in cells caused cell rounding with a concomitant loss of cell adhesion that is dependent upon the channel of the protein but not its kinase activities. Knockdown of m-calpain blocked TRPM7-induced cell rounding and cell detachment. Silencing of TRPM7 by RNA interference, however, strengthened cell adhesion and increased the number of peripheral adhesion complexes in the cells. Together, our results suggest that the ion channel TRPM7 regulates cell adhesion through m-calpain by mediating the local influx of calcium into peripheral adhesion complexes.

Highlights

The passage of Mg2ϩ by TRPM7 has linked it to the regulation of magnesium homeostasis in mammalian cells [19]
TRPM7 Colocalizes with m-Calpain to Peripheral Vinculin-containing Adhesion Complexes—We found that when TRPM7 was heterologously expressed at concentrations below the threshold required to cause cell rounding, the channel colocalized with m-calpain into clusters at the tips or ends of cellular protrusions emanating from the cell body of HEK-293 cells (Fig. 6B)
In this study we have identified m-calpain as a key effector of TRPM7 in regulating cell adhesion

Summary

Introduction

The passage of Mg2ϩ by TRPM7 has linked it to the regulation of magnesium homeostasis in mammalian cells [19]. We found that expression of TRPM7 in HEK-293 cells produced cell rounding and a loss of cell adhesion that was dependent upon m-calpain.

Results

Conclusion