Role of melanocortin receptor accessory proteins in the function of zebrafish melanocortin receptor type 2.
In this paper, we identify three different MRAPs in zebrafish, zfMRAP1, zfMRAP2a and zfMRAP2b, and demonstrate that zfMC2R is not functional in the absence of MRAP expression. ZfMRAP1 expression was restricted to adipose tissue and the anterior kidney whereas MRAP2a and MRAP2b were expressed in all the tissues tested. Quantification of surface receptor and immunofluorescence studies indicated that the receptor is unable to translocate to membrane in the absence of MRAP isoforms. MRAP1 and MRAP2b are localized in the plasma membrane in the absence of zfMC2R expression but MRAP2b is retained in perinuclear position. MRAP1 and MRAP2a displayed an equivalent translocation capacity to the membrane of zfMC2R but only zfMRAP1 expression led to intracellular cAMP increases after ACTH stimulation. ZfMRAP2b had no effect on zfMC2R activity but both zfMRAP2 isoforms enhanced the zfMRAP1-assisted cAMP intracellular increase, suggesting an interaction between zfMRAP1 and zfMRAP2s when regulating zfMC2R activity.
Agulleiro
Maria Josep
MJ
Department of Fish Physiology and Biotechnology, Instituto de Acuicultura de Torre de la Sal, Consejo Superior de Investigaciones Científicas, Ribera de Cabanes, Castellón, Spain.
Roy
Simon
S
Sánchez
Elisa
E
Puchol
Sara
S
Gallo-Payet
Nicole
N
Cerdá-Reverter
José Miguel
JM
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D044103:Receptor, Melanocortin, Type 2; D029961:Zebrafish Proteins; D000242:Cyclic AMP