Localization and diffusion of glucagon receptor in rat hepatocytes.
The lateral diffusion rate of glucagon receptor in rat hepatocyte plasma membrane in the absence and presence of glucagon was measured to be approximately 7.0 x 10(-10) cm2/s. The percentage of glucagon receptor molecules remaining on the cell surface after the activation of signal transduction process by 100 nM glucagon was approximately 74% of its original number. Although the number of glucagon receptors on the plasma membrane capable of interacting with its signal transduction partners decreases on addition of glucagon, the lateral diffusion rate and the percentage of mobile receptors remain essentially unchanged. A hypothesis has been developed that for signal transduction to occur, the random diffusion-dependent collision of one, two, or all three components is an essential part, and it may be the rate-limiting step. An approximate calculation has been made of random diffusion-dependent theoretical and experimental collision frequencies using experimentally measured concentrations and reasonable value for diffusion rate of G protein to investigate the role of diffusion in signal transduction. These calculations indicate that the diffusion of individual components is important and may be the rate-limiting step in the signal transduction process. The diffusion rate and percent mobile fraction of glucagon receptor data presented in this article are the first step toward elucidating the validity of the diffusion-dependent signal transduction hypothesis.
Gupte
S S
SS
Department of Biochemistry, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004058:Diffusion / Q000187:drug effects; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology*; D008055:Lipids; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D015335:Molecular Probes; D011485:Protein Binding; D051381:Rats; D018027:Receptors, Glucagon / Q000302:isolation & purification / Q000378:metabolism*; D015398:Signal Transduction
D008055:Lipids; D015335:Molecular Probes; D018027:Receptors, Glucagon; D005934:Glucagon; D000262:Adenylyl Cyclases