Rab3 reversibly recruits rabphilin to synaptic vesicles by a mechanism analogous to raf recruitment by ras

被引:121
作者
Stahl, B
Chou, JH
Li, C
Sudhof, TC
Jahn, R
机构
[1] YALE UNIV, SCH MED, DEPT BIOL, NEW HAVEN, CT 06510 USA
[2] YALE UNIV, SCH MED, DEPT CELL BIOL, NEW HAVEN, CT 06510 USA
[3] YALE UNIV, SCH MED, HOWARD HUGHES MED INST, BOYER CTR MOLEC MED, NEW HAVEN, CT 06510 USA
[4] UNIV TEXAS, SW MED CTR, DEPT MOLEC GENET, DALLAS, TX 75235 USA
[5] UNIV TEXAS, SW MED CTR, HOWARD HUGHES MED INST, DALLAS, TX 75235 USA
关键词
rabphilin; rab3; raf; ras; synaptic vesicles;
D O I
10.1002/j.1460-2075.1996.tb00529.x
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
GTP activates the interaction between the synaptic vesicle proteins rabphilin and rab3. This raises the question of whether rabphilin is a resident vesicle protein that recruits rab3 in a stage-dependent fashion, or if it is instead an effector protein recruited by rab3. We now show that rabphilin, like rab3, dissociates from synaptic vesicles after exocytosis in a manner requiring both Ca2+ and membrane fusion. Rabphilin interacts with GTP-rab3 via a N-terminal domain comprising a novel Zn2+-finger moth, and this interaction is essential for rabphilin binding to synaptic vesicles. Thus, in the same way that ras recruits raf to the plasma membrane, rab3 reversibly recruits rabphilin to synaptic vesicles in a stage-dependent manner. These results reveal an unexpected similarity between;the molecular mechanisms by which small G proteins function in recruiting effector proteins to membranes during membrane traffic and signal transduction.
引用
收藏
页码:1799 / 1809
页数:11
相关论文
共 75 条
[1]  
ARAKI S, 1990, J BIOL CHEM, V265, P13007
[2]   MEMBRANE TARGETING OF THE NUCLEOTIDE EXCHANGE FACTOR SOS IS SUFFICIENT FOR ACTIVATING THE RAS SIGNALING PATHWAY [J].
ARONHEIM, A ;
ENGELBERG, D ;
LI, NX ;
ALALAWI, N ;
SCHLESSINGER, J ;
KARIN, M .
CELL, 1994, 78 (06) :949-961
[3]   RAF MEETS RAS - COMPLETING THE FRAMEWORK OF A SIGNAL-TRANSDUCTION PATHWAY [J].
AVRUCH, J ;
ZHANG, XF ;
KYRIAKIS, JM .
TRENDS IN BIOCHEMICAL SCIENCES, 1994, 19 (07) :279-283
[4]  
BOURNE HR, 1991, NATURE, V349, P117, DOI 10.1038/349117a0
[5]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[6]   2 DISTINCT RAF DOMAINS MEDIATE INTERACTION WITH RAS [J].
BRTVA, TR ;
DRUGAN, JK ;
GHOSH, S ;
TERRELL, RS ;
CAMPBELLBURK, S ;
BELL, RM ;
DER, CJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (17) :9809-9812
[7]  
BURSTEIN ES, 1991, J BIOL CHEM, V266, P2689
[8]  
BURSTEIN ES, 1993, J BIOL CHEM, V268, P22247
[9]   CA2+-DEPENDENT RECYCLING OF SYNAPTIC VESICLES AT THE FROG NEUROMUSCULAR-JUNCTION [J].
CECCARELLI, B ;
HURLBUT, WP .
JOURNAL OF CELL BIOLOGY, 1980, 87 (01) :297-303
[10]   HUMAN SOS1 - A GUANINE-NUCLEOTIDE EXCHANGE FACTOR FOR RAS THAT BINDS TO GRB2 [J].
CHARDIN, P ;
CAMONIS, JH ;
GALE, NW ;
VANAELST, L ;
SCHLESSINGER, J ;
WIGLER, MH ;
BARSAGI, D .
SCIENCE, 1993, 260 (5112) :1338-1343