Ozaki N, Shibasaki T, Kashima Y, Miki T, Takahashi K, Ueno H, Sunaga Y, Yano H, Matsuura Y, Iwanaga T, Takai Y, Seino S
Department of Molecular Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Nat Cell Biol. 2000 Nov;2(11):805-11. doi: 10.1038/35041046.
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.
尽管环磷酸腺苷(cAMP)在许多分泌细胞中调节胞吐作用已广为人知,但其在胞吐机制中的直接靶点尚不清楚。在此我们表明,一种cAMP传感器cAMP-GEFII与Rim(Rab3相互作用分子,Rab3是一种小G蛋白)以及一种新的异构体Rim2结合,这两者均为囊泡与质膜融合的假定调节因子。我们还表明,cAMP-GEFII通过与Rim2相互作用,介导cAMP诱导的、Ca2+依赖的分泌,而这种分泌不受cAMP依赖性蛋白激酶(PKA)抑制剂的阻断。因此,cAMP-GEFII是调节性胞吐作用中cAMP的直接靶点,并且负责cAMP依赖的、PKA非依赖的胞吐作用。