title: CAP2 is a regulator of the actin cytoskeleton and its absence changes infiltration of inflammatory cells and contraction of wounds.
abstract: Cyclase associated protein (CAP) is a highly conserved protein with roles in actin dynamics and many cellular processes. Two isoforms exist in higher eukaryotes, CAP1 and CAP2. CAP1 is ubiquitously expressed whereas CAP2 shows restricted tissue distribution. In mice, ablation of CAP2 leads to development of cardiomyopathy. CAP2 is expressed in skin. In human skin its expression is increased in wounds. To elucidate the role of CAP2 in skin upon injury, we studied the wound healing in CAP2 deficient mice and found altered wound healing response presumably resulting from reduced levels of α-SMA, decreased macrophage infiltration and slower neovascularization. In vitro cultured Cap2 deficient keratinocytes showed reduced velocity and a delay in scratch closure. The analysis of primary mutant fibroblasts also showed reduced velocity and less contractibility. They had extended protrusions and more focal adhesions. In addition the F-actin content was increased keeping the total actin content unaltered. Mutant fibroblasts furthermore exhibited an altered response during recovery from drug-induced disruption of the actin cytoskeleton. Interestingly, CAP1 was upregulated in knockout unwounded skin and in wounds which might partially compensate for the loss of CAP2. Taken together, our studies reveal a role for CAP2 in wound healing which may be based on its function as a regulator of the actin cytoskeleton.
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Kosmas
authors.initials: K
authors.lastname: Kosmas
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Eskandarnaz
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Arya B
authors.initials: AB
authors.lastname: Khorsandi
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Atul
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Ranjan
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Department of Dermatology, University of Cologne, Cologne, Germany.
authors.forename: Sabine A
authors.initials: SA
authors.lastname: Eming
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Angelika A
authors.initials: AA
authors.lastname: Noegel
authors.affiliation: Institute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. Electronic address: pechev@uni-koeln.de.
authors.forename: Vivek S
authors.initials: VS
authors.lastname: Peche
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D055786:Gene Knockout Techniques; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D012867:Skin / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D014947:Wounds and Injuries / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins; D048868:Adaptor Proteins, Signal Transducing
chemical_list: D002352:Carrier Proteins; C525400:Cap2 protein, mouse; D008565:Membrane Proteins; D048868:Adaptor Proteins, Signal Transducing
keywords: Actin; Actin binding proteins; CAP1; Cell migration; Cyclase associated protein; Wound healing