Ca2+/calmodulin-binding peptides block phototransduction in Limulus ventral photoreceptors: evidence for direct inhibition of phospholipase C.
Phototransduction in Limulus photoreceptors involves a G protein-mediated activation of phospholipase C (PLC) and subsequent steps involving InsP3-mediated release of intracellular Ca2+. While exploring the role of calmodulin in this cascade, we found that intracellular injection of Ca2+/calmodulin-binding peptides (CCBPs) strongly inhibited the light response. By chemically exciting the cascade at various stages, we found the primary target of this effect was not in late stages of the cascade but rather at the level of G protein and PLC. That PLCdelta1 contains a calmodulin-like structure raised the possibility that PLC might be directly affected by CCBPs. To test this possibility, in vitro experiments were conducted on purified PLC. The activity of this enzyme was strongly inhibited by CCBPs and also inhibited by calmodulin itself. Our results suggest that the calmodulin-like region of PLC has an important role in regulating this enzyme.
Richard
E A
EA
Biology, Brandeis University, Waltham, MA 02254-9110, USA.
Ghosh
S
S
Lowenstein
J M
JM
Lisman
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D002147:Calmodulin / Q000378:metabolism / Q000494:pharmacology; D002148:Calmodulin-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006737:Horseshoe Crabs / Q000378:metabolism* / Q000528:radiation effects*; D066298:In Vitro Techniques; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D017956:Photoreceptor Cells, Invertebrate / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D004791:Enzyme Inhibitors; D010455:Peptides; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins