Caldesmon: a bifunctional (calmodulin and actin) binding protein which regulates stimulated gonadotropin release.
Calmodulin (CaM) serves as an intracellular Ca2+ receptor in the gonadotrope and appears to mediate GnRH-stimulated gonadotropin release. Recently we have specifically identified three CaM binding proteins of the gonadotrope as calcineurin, caldesmon, and spectrin. Caldesmon (identified by seven polyclonal and a monoclonal antibody, as well as by functional characteristics) appears to be a CaM-regulated, F-actin binding, protein. This 84,000 mol wt component (CaD84) is heat stable and cosediments with F-actin in the absence of Ca2+. In the presence of Ca2+ (greater than 1 microM) this protein disassociates from F-actin and reassociates with calmodulin. We have prepared an antibody which blocks the caldesmon-actin interaction. In the present study, we have loaded this antibody into cells to prevent the (re-)association of caldesmon with F-actin. This treatment synergistically augments the ability of GnRH and other secretogogues (maitotoxin, phorbol myristyl acetate) to stimulate gonadotropin release from the pituitary. This finding, along with the previous observations that GnRH provokes a sufficient rise in intracellular Ca2+ to allow CaM to redistribute and bind proteins which it regulates, suggests a role for caldesmon in GnRH-stimulated gonadotropin release from the pituitary.
Janovick
J A
JA
Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242-1109.
Natarajan
K
K
Longo
F
F
Conn
P M
PM
D000199:Actins / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D002645:Chickens; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000199:Actins; D000906:Antibodies; D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D007987:Gonadotropin-Releasing Hormone; D004533:Egtazic Acid; D007986:Luteinizing Hormone; D002118:Calcium