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Swaminathan, Karthic; Stumpf, Maria; Müller, Rolf; Horn, Anna-Carolin; Schmidbauer, Julia; Eichinger, Ludwig; Müller-Taubenberger, Annette; Faix, Jan and Noegel, Angelika A. (2015): Coronin7 regulates WASP and SCAR through CRIB mediated interaction with Rac proteins. In: Scientific Reports, Vol. 5, 14437 [PDF, 2MB]

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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.

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