cAMP-GEFII is a direct target of cAMP in regulated exocytosis.
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.
Ozaki
N
N
Department of Molecular Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Shibasaki
T
T
Kashima
Y
Y
Miki
T
T
Takahashi
K
K
Ueno
H
H
Sunaga
Y
Y
Yano
H
H
Matsuura
Y
Y
Iwanaga
T
T
Takai
Y
Y
Seino
S
S
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
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