title: Physiological role of the interaction between CARMIL1 and capping protein.
abstract: The regulation of free barbed ends is central to the control of dynamic actin assembly and actin-based motility in cells. Capping protein (CP) is known to regulate barbed ends and control actin assembly in cells. The CARMIL family of proteins can bind and inhibit CP in vitro, but the physiological significance of the interaction of CARMIL with CP in cells is poorly understood. Mammalian cells lacking CARMIL1 have defects in lamellipodia, macropinocytosis, cell migration, and Rac1 activation. Here we investigate the physiological significance of the CARMIL1-CP interaction, using a point mutant with a well-defined biochemical defect. We find that the CARMIL1-CP interaction is essential for the assembly of lamellipodia, the formation of ruffles, and the process of macropinocytosis. In contrast, the interaction of CARMIL1 with CP shows little to no importance for other functions of CARMIL1, including localization of CARMIL1 to the membrane, activation of Rac1, and cell migration. One implication is that lamellipodia are only marginally important for cell migration in a wound-healing model. The results also suggest that the ability of CARMIL1 to inhibit CP in cells may be regulated.
authors.affiliation: Department of Cell Biology and Physiology, Washington University in St. Louis, St. Louis, MO 63110.
authors.forename: Marc
authors.initials: M
authors.lastname: Edwards
authors.forename: Yun
authors.initials: Y
authors.lastname: Liang
authors.forename: Taekyung
authors.initials: T
authors.lastname: Kim
authors.forename: John A
authors.initials: JA
authors.lastname: Cooper
mesh_terms: D051344:Actin Capping Proteins / Q000737:chemistry / Q000378:metabolism*; D020816:Amino Acid Motifs; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics*; D006801:Humans; D008840:Microfilament Proteins; D010873:Pinocytosis / Q000235:genetics; D017354:Point Mutation; D011485:Protein Binding; D011554:Pseudopodia / Q000378:metabolism / Q000473:pathology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D051344:Actin Capping Proteins; C547525:CARMIL1 protein, human; D002352:Carrier Proteins; D008840:Microfilament Proteins; C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein
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