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Molecular Biology of the Cell Vol. 17, 239250, January 2006

Summary: Molecular Biology of the Cell
Vol. 17, 239­250, January 2006
Proteolysis of Cortactin by Calpain Regulates Membrane
Protrusion during Cell MigrationD
Benjamin J. Perrin,* Kurt J. Amann,
and Anna Huttenlocher
*Cellular and Molecular Biology Program,
Department of Zoology and Laboratory of Molecular Biology and

Department of Pediatrics and Pharmacology, University of Wisconsin­Madison, Madison, WI 53706
Submitted June 3, 2005; Revised October 25, 2005; Accepted October 31, 2005
Monitoring Editor: Martin A. Schwartz
Calpain 2 regulates membrane protrusion during cell migration. However, relevant substrates that mediate the effects of
calpain on protrusion have not been identified. One potential candidate substrate is the actin binding protein cortactin.
Cortactin is a Src substrate that drives actin polymerization by activating the Arp2/3 complex and also stabilizes the
cortical actin network. We now provide evidence that proteolysis of cortactin by calpain 2 regulates membrane protrusion
dynamics during cell migration. We show that cortactin is a calpain 2 substrate in fibroblasts and that the preferred
cleavage site occurs in a region between the actin binding repeats and the -helical domain. We have generated a mutant
cortactin that is resistant to calpain proteolysis but retains other biochemical properties of cortactin. Expression of the
calpain-resistant cortactin, but not wild-type cortactin, impairs cell migration and increases transient membrane protru-


Source: Amann, Kurt - Molecular and Cellular Pharmacology Training Program & Department of Zoology, University of Wisconsin at Madison


Collections: Biology and Medicine