Isolation and characterization of a dual prenylated Rab and VAMP2 receptor

被引:102
作者
Martincic, I [1 ]
Peralta, ME [1 ]
Ngsee, JK [1 ]
机构
[1] UNIV OTTAWA,LOEB RES INST,DEPT MED & BIOCHEM,OTTAWA,ON K1Y 4E9,CANADA
关键词
D O I
10.1074/jbc.272.43.26991
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Rab GTPases have been implicated in intracellular vesicle trafficking. Using the yeast two-hybrid screen, we have isolated a rat clone that interacts with Rab3A as well as with Rab1. The gene encodes a 20.6-kDa protein with two extensive hydrophobic domains and is broadly expressed in all tissues. This protein binds to prenylated Rab GTPases but not to other small Ras like GTPases such as the Rho/Rac family. This prenylated Rab acceptor (PRA1) also binds specifically to the synaptic vesicle protein VAMPS (or synaptobrevin II) but shows no affinity for VAMP1 or cellubrevin in both the yeast two-hybrid system and in vitro binding assays. This specificity resides, in part, in the proline-rich domain of VAMPS as a chimera containing this domain of VAMPS fused to VAMP1 is able to bind to PRA1. The transmembrane domain of VAMPS is also essential as its deletion abolished binding to PRA1. Replacement of the deleted VAMPS transmembrane domain by a CAAX prenylation signal can not restore binding to PRA1. This interaction is therefore distinct from that required for VAMPS binding to either syntaxin or both syntaxin and SNAP-25, Deletion analysis on PRA1 indicates that the critical Rab-and VAMP2-interacting residues reside in two regions: the amino-terminal residues 30-54 and the extreme carboxyl-terminal domain. This dual Rab and VAMPS binding characteristic suggests that PRA1 may serve to link these two protein families in the control of vesicle docking and fusion.
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页码:26991 / 26998
页数:8
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