The Shank family of postsynaptic density proteins interacts with and promotes synaptic accumulation of the βPIX guanine nucleotide exchange factor for Rac1 and Cdc42

被引:132
|
作者
Park, E
Na, M
Choi, JH
Kim, S
Lee, JR
Yoon, JY
Park, D
Sheng, M
Kim, E [1 ]
机构
[1] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea
[2] Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea
[3] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA
[4] MIT, RIKEN MIT Neurosci Res Ctr, Picower Ctr Learning & Memory, Cambridge, MA 02139 USA
关键词
D O I
10.1074/jbc.M301052200
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
The Shank/ProSAP family of multidomain proteins is known to play an important role in organizing synaptic multiprotein complexes. Here we report a novel interaction between Shank and betaPIX, a guanine nucleotide exchange factor for the Rac1 and Cdc42 small GTPases. This interaction is mediated by the PDZ domain of Shank and the C-terminal leucine zipper domain and the PDZ domain-binding motif at the extreme C terminus of betaPIX. Shank colocalizes with betaPIX at excitatory synaptic sites in cultured neurons. In brain, Shank forms a complex with betaPIX and betaPIX-associated signaling molecules including p21-associated kinase (PAK), an effector kinase of Rac1/Cdc42. Importantly, overexpression of Shank in cultured neurons promotes synaptic accumulation of betaPIX and PAK. Considering the involvement of Rac1 and PAK in spine dynamics, these results suggest that Shank recruits betaPIX and PAK to spines for the regulation of postsynaptic structure.
引用
收藏
页码:19220 / 19229
页数:10
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