How do invadopodia disassemble?2018-02-06T10:46:10+00:00

How do invadopodia disassemble?

The final step in function of invadopodia is disassembly which primarily involves dismantling the actin core [1]. Several proteins have been implicated in a cascade leading to this, including paxillin, extracellular signal-regulated kinases (Erk) and calpain [1]. The phosphorylation state of tyrosine residues within paxillin localized to invadopodia controls the rate of disassembly. The mutation of specific tyrosine residues in paxillin render these sites non-phosphorylatable and this results in a significant delay in the disassembly of invadopodia. Furthermore, phosphorylation of paxillin was shown to promote the activation of Erk, which promotes the activation of calpain [1]. Calpains are calcium dependent, non-lysosomal, cysteine proteases. The activation of calpain 2 has been shown to be required for the degradation of cortactin, a component of the actin core and this subsequently promotes invadopodia disassembly [2]. The inhibition of calpain [1] or the expression of calpain-resistant cortactin in cells lacking endogenous cortactin [2], results in a decrease in the rate of invadopodia disassembly. This is akin to the role of calpain in the degradation of talin [3] and focal adhesion kinase [4], which has been shown to promote focal adhesion disassembly.

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  1. Badowski C, Pawlak G, Grichine A, Chabadel A, Oddou C, Jurdic P, Pfaff M, Albigès-Rizo C, and Block MR. Paxillin phosphorylation controls invadopodia/podosomes spatiotemporal organization. Mol. Biol. Cell 2007; 19(2):633-45. [PMID: 18045996]
  2. McMaster OG, Du F, French ED, and Schwarcz R. Focal injection of aminooxyacetic acid produces seizures and lesions in rat hippocampus: evidence for mediation by NMDA receptors. Exp. Neurol. 1991; 113(3):378-85. [PMID: 1833221]
  3. Franco SJ, Rodgers MA, Perrin BJ, Han J, Bennin DA, Critchley DR, and Huttenlocher A. Calpain-mediated proteolysis of talin regulates adhesion dynamics. Nat. Cell Biol. 2004; 6(10):977-83. [PMID: 15448700]
  4. Chan KT, Bennin DA, and Huttenlocher A. Regulation of adhesion dynamics by calpain-mediated proteolysis of focal adhesion kinase (FAK). J. Biol. Chem. 2010; 285(15):11418-26. [PMID: 20150423]