title: PACAP induces the dimerization of PAC1 on the nucleus associated with the cAMP increase in the nucleus.
abstract: PAC1 is PACAP (pituitary adenylate cyclase-activating polypeptide) preferring receptor belonging to class B G protein couple receptor (GPCR) mediating the most effects of PACAP. The dimerization of PAC1 has been proven by our previous research. The bimolecular fluorescence complementation (BiFC) combined with fluorescence confocal microscope image was used in this research to explore the profiles of PAC1 dimers during the activation by PACAP. Fluorescence metry and cAMP assays were both used to detect the functions of the dimerization of PAC1 on the nucleus induced by PACAP. It was found that PACAP in concentration lower than 10nM induced the de-dimerization of PAC1 on the plasma membranes and the re-dimerization of PAC1 on the nucleus. While PACAP in concentration higher than 10nM, the nuclear localized PAC1 dimers were further translocated from outside/on the nucleus into the nucleus. In addition, it was also found that the more PAC1 dimers on the nucleus produced the higher cAMP level in the nucleus, and the levels of cAMP in the nucleus varied synchronously with functions of PACAP on the proliferation of PAC1-CHO cells. These results indicated the dimerization of PAC1 on the nucleus may be involved in the cell signals produced by PACAP. The finding and the research on the dimerization of PAC1 on the nucleus will help us to step forward to clarify the physiological and pharmacological role of PAC1.
authors.affiliation: The Cell Biology Institute, The Department of Cell Biology, Jinan University, Guangzhou 510632, China. rongjie_yu1123@163.com
authors.forename: Rongjie
authors.initials: R
authors.lastname: Yu
authors.forename: Jiaping
authors.initials: J
authors.lastname: Zhong
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Guo
authors.forename: Huahua
authors.initials: H
authors.lastname: Zhang
authors.forename: Jianhuan
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000378:metabolism*
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D000242:Cyclic AMP
keywords: Dimerization; GPCR; Nuclear; PAC1; PACAP