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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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COS Cells
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Carrier Proteins
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Chlorocebus aethiops
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Cyclic AMP / metabolism*
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Cyclic AMP Receptor Protein / genetics
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Cyclic AMP Receptor Protein / metabolism*
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Cyclic AMP-Dependent Protein Kinases / metabolism
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DNA, Complementary
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Exocytosis / physiology*
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GTP-Binding Proteins*
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Mice
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Molecular Sequence Data
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Rats
Substances
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Carrier Proteins
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Cyclic AMP Receptor Protein
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DNA, Complementary
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Nerve Tissue Proteins
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Rim protein, mammalian
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Rims1 protein, mouse
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Rims1 protein, rat
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Rims2 protein, mouse
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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GTP-Binding Proteins
Associated data
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GENBANK/AB021131
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GENBANK/AB021132