TY  - JOUR
A1  - Jesaitis, A. J.
A1  - Klotz, Karl-Norbert
T1  - Cytoskeletal regulation of chemotactic receptors: Molecular complexation of N-formyl peptide receptors with G proteins and actin
N2  - Signal transduction via receptors for N-formylmethionyl peptide chemoattractants (FPR) on human neutrophils is a highly regulated process. It involves direct interaction of receptors with heterotrimeric G-proteins and may be under thc control of cytoskeletal clemcnts. Evidencc exists suggesting that thc cytoskeleton and/or the membrane ske1eton determines the distribution of FPR in the plane of the plasma membrane, thus controlling FPR accessibility to different protcins in functionally distinct membrane domains. In desensitized cells, FPR are restricted to domains which are depleted of G proteins but enriched in cytoskeletal proteins such as actin and fodrin. Thus, the G protein signal transduction partners of FPR become inacccssible to the agonist-occupied receptor, preventing cell activation. We are investigating the molecular 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.
KW  - Immunologie
KW  - chemotaxis
KW  - formyl peptides
KW  - receptors
KW  - actin
KW  - G proteins
KW  - cytoskeleton
KW  - membrane skeleton
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-79673
ER  - 
TY  - JOUR
A1  - Klotz, Karl-Norbert
A1  - Jesaitis, A. J.
T1  - The interaction of N-formyl peptide chemoattractant receptors with the membrane skeleton is energy-dependent
N2  - Desensitization of N-fonnyl peptide chemoattractant receptors (FPR) in human neutrophils is thought to be achieved by lateral segregation of receptors and G proteins within the plane of the plasma membrane resulting in an interruption of the signalling cascade. Direct coupling of FPR to membrane skeletal actin appears to be the basis of this process~ however, the molecular mechanism is unknown. In this study we investigated the effect of energy depletion on formation of FPR-membrane skeleton complexes. In addition the effect of the protein kinase C inhibitor stauroporine and the phosphatase inhibitor okadaic acid on coupling of FPR to the membrane skeletonwas studied. Human neutrophils were desensitized using the photoreactive agonist N-formy1-met-leu-phe-1ys-N'[\(^{125}\)I]2(p-azidosalicylamido)ethyl-1,3'-dithiopropionate (fMLFK-[\(^{125}\)I]ASD) after ATP depletion with NaF or after incubation with the respective inhibitors. The interaction of FPR with the membrane skeleton was studied by Sedimentation of the membrane skeleton-associated receptors in sucrose density gradients. Energy depletion of the cells markedly inhibited the formation of FPR-membrane skeleton complexes. This does not appear tobe related to inhibition of protein phosphorylation due to ATP depletion because inhibition of protein kinases and phosphatases bad no significant effect on coupling of FPR to the membrane skeleton. We conclude, therefore, that coupling of FPR to the membrane skeleton is an energy,dependent process which does not appear to require modification of the receptor protein by phosphorylation.
KW  - Toxikologie
KW  - Chemotactic receptors
KW  - G proteins
KW  - N-formyl peptides
KW  - signal transduction
KW  - desensitization
KW  - membrane skeleton
KW  - receptor-G protein coupling.
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60499
ER  -