Calmodulin interacts with PAC1 and VPAC2 receptors and regulates PACAP-induced FOS expression in human neuroblastoma cells.
The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) mediates its physiological functions through activation of PAC1, VPAC1 and VPAC2 receptors, and the ubiquitous Ca(2+)-sensor calmodulin has been implicated in PACAP-induced signaling. The immediate early response gene FOS is a well-known marker of neuronal activation, so we used a human neuroblastoma cell line NB-1 to explore the role of calmodulin in PACAP-induced FOS gene expression. We observed both short-term and prolonged altered PACAP-mediated activation of the FOS gene in the presence of the calmodulin-antagonist W-7. NB-1 cells were shown to express PAC1 and VPAC2 receptors, and immunoprecipitation of both receptors displayed a co-association with calmodulin in the absence of Ca(2+). Our findings indicate a novel mechanism of calmodulin in regulating PACAP signaling by possible interaction with the inactive state of PAC1 and VPAC2 receptors.
Falktoft
Birgitte
B
Department of Clinical Biochemistry, Bispebjerg Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. bf11@bbh.regionh.dk
Georg
Birgitte
B
Fahrenkrug
Jan
J
D002147:Calmodulin / Q000378:metabolism* / Q000502:physiology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000378:metabolism*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
C495401:ADCYAP1 protein, human; D002147:Calmodulin; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016760:Proto-Oncogene Proteins c-fos; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I