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.
Highlights
Coronins are a large family of evolutionary conserved proteins
Of these only four positions are conserved in the Cdc42/Rac interactive binding (CRIB) domains of CRN7 (Fig. 1ab)
Adjacent sequences contribute to the binding, and less well conserved CRIB domains lead to successful GTPase interactions
Summary
Coronins are a large family of evolutionary conserved proteins They consist of a WD (TryptophaneAspartate)-repeat domain containing seven repeats that form a seven-bladed β -propeller structurally resembling the Gβ subunit of the heterotrimeric G-proteins. Mutants lacking the protein exhibit enhanced phagocytosis of yeast particles, defective cell substratum adhesion, motility and enhanced development letting us conclude that coronin[7] has an inhibitory impact on these processes[7,12]. This inhibitory action could be achieved through the direct F-actin interaction and/or through controlling F-actin dynamics by affecting cytoskeletal regulators like Rac proteins and their effectors
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