title: cAMP-GEFII is a direct target of cAMP in regulated exocytosis.
abstract: Although cAMP is well known to regulate exocytosis in many secretory cells, its direct target in the exocytotic machinery is not known. Here we show that cAMP-GEFII, a cAMP sensor, binds to Rim (Rab3-interacting molecule, Rab3 being a small G protein) and to a new isoform, Rim2, both of which are putative regulators of fusion of vesicles to the plasma membrane. We also show that cAMP-GEFII, through its interaction with Rim2, mediates cAMP-induced, Ca2+-dependent secretion that is not blocked by an inhibitor of cAMP-dependent protein kinase (PKA). Accordingly, cAMP-GEFII is a direct target of cAMP in regulated exocytosis and is responsible for cAMP-dependent, PKA-independent exocytosis.
authors.affiliation: Department of Molecular Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Ozaki
authors.forename: T
authors.initials: T
authors.lastname: Shibasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Kashima
authors.forename: T
authors.initials: T
authors.lastname: Miki
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Ueno
authors.forename: Y
authors.initials: Y
authors.lastname: Sunaga
authors.forename: H
authors.initials: H
authors.lastname: Yano
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuura
authors.forename: T
authors.initials: T
authors.lastname: Iwanaga
authors.forename: Y
authors.initials: Y
authors.lastname: Takai
authors.forename: S
authors.initials: S
authors.lastname: Seino
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002352:Carrier Proteins; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000378:metabolism*; D002373:Cyclic AMP Receptor Protein / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018076:DNA, Complementary; D005089:Exocytosis / Q000502:physiology*; D019204:GTP-Binding Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats
chemical_list: D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; C107293:Rim protein, mammalian; C491490:Rims1 protein, mouse; C491489:Rims1 protein, rat; C491491:Rims2 protein, mouse; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins