CYTOSKELETAL REGULATION OF CHEMOTACTIC RECEPTORS - MOLECULAR COMPLEXATION OF N-FORMYL PEPTIDE RECEPTORS WITH G-PROTEINS AND ACTIN

Signal transduction via receptors for N-formylmethionyl peptide chemoa ttractants (FPR) on human neutrophils is a highly regulated process. I t involves direct interaction of receptors with heterotrimeric G-prote ins and may be under the control of cytoskeletal elements. Evidence ex ists suggesting that the cytoskeleton and/or the membrane skeleton det ermines the distribution of FPR in the plane of the plasma membrane, t hus controlling FPR accessibility to different proteins in functionall y distinct membrane domains. In desensitized cells, FPR are restricted to domains which are depleted of G proteins but enriched in cytoskele tal proteins such as actin and fodrin. Thus, the G protein signal tran sduction partners of FPR become inaccessible to the agonist-occupied r eceptor, preventing cell activation. We are investigating the molecula r basis for the interaction of FPR with the membrane skeleton, and our results suggest that FPR, and possibly other receptors, may directly bind to cytoskeletal proteins such as actin.