Combinatorial morphogenesis of dendritic spines and filopodia by SPAR and alpha-actinin2.

Combinatorial morphogenesis of dendritic spines and filopodia by SPAR and alpha-actinin2.
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DOI:
10.1016/j.bbrc.2009.04.069
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发表时间:
2009-06-19
影响因子:
3.1
通讯作者:
Pak, Daniel T. S.
Pak, Daniel T. S.
中科院分区:
生物学4区
文献类型:
--
作者:
Hoe, Hyang-Sook;Lee, Ji-Yun;Pak, Daniel T. S.

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RAP小GTP酶调节树突棘的兴奋性突触强度和形态可塑性。脊柱结构的改变是由F-肌动蛋白细胞骨架介导的,但Rap活性和肌动蛋白动力学之间的联系尚不清楚。在这里,我们报道了RAP的突触后抑制物SPAR和肌动蛋白交联蛋白家族α-肌动蛋白之间的一种新的相互作用。Spar和α-Actinin参与了树突棘的双向结构可塑性:Spar促进脊柱头部增大,而α-Actinin2表达增加有利于树突棘的伸长和变薄。令人惊讶的是,Spar和α-actinin2在同一树突棘上能够以相加而不是拮抗的方式发挥作用,产生组合的刺/丝足杂交种。这些数据确定了在突触连接肌动蛋白细胞骨架和Rap的分子途径,并表明棘突和丝足的形成不一定是结构可塑性的相反形式。
Rap small GTPases regulate excitatory synaptic strength and morphological plasticity of dendritic spines. Changes in spine structure are mediated by the F-actin cytoskeleton, but the link between Rap activity and actin dynamics is unclear. Here we report a novel interaction between SPAR, a postsynaptic inhibitor of Rap, and α-actinin, a family of actin-crosslinking proteins. SPAR and α-actinin engage in bidirectional structural plasticity of dendritic spines: SPAR promotes spine head enlargement, whereas increased α-actinin2 expression favors dendritic spine elongation and thinning. Surprisingly, SPAR and α-actinin2 can function in an additive rather than antagonistic fashion at the same dendritic spine, generating combination spine/filopodia hybrids. These data identify a molecular pathway bridging the actin cytoskeleton and Rap at synapses, and suggest that formation of spines and filopodia are not necessarily opposing forms of structural plasticity.
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