The characterization of collapsin response mediator protein-1 (CRMP-1) for Arp2/3 dependent actin structures
The actin cytoskeleton, composed of actin and its binding proteins, drives cell motility, determines cell shape, and is necessary for strong cell-matrix and cell-cell adhesion. Consistent with its critical function in cell physiology, actin assembly is highly regulated. One of the key factors controlling actin assembly is the actin nucleator, the Arp2/3 complex. Upon the hierarchical regulation of the activity of the Arp2/3 complex, the cell can build the correct actin framework spatially and temporally in response to different cellular signals. Understanding the molecular mechanism of how Arp2/3 is regulated would provide crucial insights into how actin polymerization is normally controlled to direct cell movements and also insights into how misregulation of actin assembly can cause disease such as metastasis. Even though many factors have been shown to contribute to Arp2/3 dependent actin assembly, these known factors are not sufficient to account for Arp2/3 mediated actin assembly detected in cells, implying there are still missing factors that contribute to this reaction. The bacterial pathogen Listeria monocytogenes, for example, uses host Arp2/3 to assemble an actin comet tail. We used Listeria as a tool to screen brain cytosol for new factors that promote comet tail assembly. We identified Collapsin Response Mediator Protein-1 (CRMP-1) as a new factor for Arp2/3 dependent actin polymerization. CRMP-1 is essential for Listeria monocytogenes actin tail formation, as well as for actin filament accumulation inside MDCK epithelial cells. CRMP-1 acts as an enhancer for Arp2/3 complex in the Listeria system; yet CRMP-1 works with EVL as a novel Arp2/3 activator in the mammalian system. Perturbing CRMP-1 function results in the loss of actin assembly in both systems. CRMP-1 belongs to CRMP family which has been long studied as a microtubule binding protein. Our results reveal a potential new role for this whole family: a factor that crosstalk between actin and microtubule cytoskeleton.
Actin cytoskeleton, Collapsin Response Mediator Protein-1, Arp2/3 complex
University of Illinois - Urbana-Champaign
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University of Illinois at Urbana-Champaign