title: Coronin7 regulates WASP and SCAR through CRIB mediated interaction with Rac proteins.
abstract: Coronin7 (CRN7) stabilizes F-actin and is a regulator of processes associated with the actin cytoskeleton. Its loss leads to defects in phagocytosis, motility and development. It harbors a CRIB (Cdc42- and Rac-interactive binding) domain in each of its WD repeat domains which bind to Rac GTPases preferably in their GDP-loaded forms. Expression of wild type CRN7 in CRN7 deficient cells rescued these defects, whereas proteins with mutations in the CRIB motifs which were associated with altered Rac binding were effective to varying degrees. The presence of one functional CRIB was sufficient to reestablish phagocytosis, cell motility and development. Furthermore, by molecular modeling and mutational analysis we identified the contact regions between CRN7 and the GTPases. We also identified WASP, SCAR and PAKa as downstream effectors in phagocytosis, development and cell surface adhesion, respectively, since ectopic expression rescued these functions.
authors.affiliation: Center for Biochemistry, Medical Faculty, Center for Molecular Medicine Cologne (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Köln, Germany.
authors.forename: Karthic
authors.initials: K
authors.lastname: Swaminathan
authors.affiliation: Center for Biochemistry, Medical Faculty, Center for Molecular Medicine Cologne (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Köln, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Stumpf
authors.affiliation: Center for Biochemistry, Medical Faculty, Center for Molecular Medicine Cologne (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Köln, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
authors.affiliation: Center for Biochemistry, Medical Faculty, Center for Molecular Medicine Cologne (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Köln, Germany.
authors.forename: Anna-Carolin
authors.initials: AC
authors.lastname: Horn
authors.affiliation: Center for Biochemistry, Medical Faculty, Center for Molecular Medicine Cologne (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Köln, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Schmidbauer
authors.affiliation: Center for Biochemistry, Medical Faculty, Center for Molecular Medicine Cologne (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Köln, Germany.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Eichinger
authors.affiliation: Institute of Anatomy and Cell Biology, Ludwig-Maximilians-University, 80336 München.
authors.forename: Annette
authors.initials: A
authors.lastname: Müller-Taubenberger
authors.affiliation: Department of Biophysical Chemistry, Medizinische Hochschule Hannover, 30623 Hannover, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Faix
authors.affiliation: Center for Biochemistry, Medical Faculty, Center for Molecular Medicine Cologne (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Köln, Germany.
authors.forename: Angelika A
authors.initials: AA
authors.lastname: Noegel
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002448:Cell Adhesion; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D056895:Mycetozoa; D010587:Phagocytosis; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D015800:Protozoan Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D008840:Microfilament Proteins; D015800:Protozoan Proteins; C491975:SCAR protein, Dictyostelium; D051316:Wiskott-Aldrich Syndrome Protein; C072061:coronin proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D020744:rac GTP-Binding Proteins