WRP/srGAP3 facilitates the initiation of spine development by an inverse F-BAR domain, and its loss impairs long-term memory.
WRP/srGAP3 facilitates the initiation of spine development by an inverse F-BAR domain, and its loss impairs long-term memory.
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DOI：
10.1523/jneurosci.4433-10.2011
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发表时间：
2011-02-16
期刊：
影响因子：
--
通讯作者：
Soderling SH
中科院分区：
文献类型：
--
作者：
Carlson BR;Lloyd KE;Kruszewski A;Kim IH;Rodriguiz RM;Heindel C;Faytell M;Dudek SM;Wetsel WC;Soderling SH
WAVE相关的Rac GAP（WRP）被认为调节突触发育和功能的关键方面，并可能与人类的智力低下有关。WRP包含一个新描述的未知函数的逆F-BAR（IF-BAR）域。我们的研究表明，这个域的感觉/促进类似于丝状伪足的向外突出，这可能是由一个凸的脂质结合表面上的WRP IF-BAR域的分子基础解释。在树突中，WRP的IF-BAR结构域在轴上形成芽，从中出现刺的前体。体内和体外WRP的丢失导致棘密度降低。在体内，这主要是蘑菇形刺的损失。在发育上，WRP功能在树突状丝状伪足普遍存在的棘发生开始时是至关重要的。最后，由于WRP与精神发育迟滞有关，因此对WRP杂合子和无效小鼠的行为进行了评价。这些研究的结果证实，WRP的丢失与学习和记忆受损有关。
The WAVE-associated Rac GAP, WRP, is thought to regulate key aspects of synapse development and function and may be linked to mental retardation in humans. WRP contains a newly described inverse F-BAR (IF-BAR) domain of unknown function. Our studies show that this domain senses/facilitates outward protrusions analogous to filopodia and that the molecular basis for this is likely explained by a convex lipid-binding surface on the WRP IF-BAR domain. In dendrites the IF-BAR domain of WRP forms a bud on the shaft from which precursors to spines emerge. Loss of WRP in vivo and in vitro results in reduced density of spines. In vivo this is primarily a loss of mushroom-shaped spines. Developmentally, WRP function is critical at the onset of spinogenesis, when dendritic filopodia are prevalent. Finally, because WRP is implicated in mental retardation, behaviors of WRP heterozygous and null mice have been evaluated. Results from these studies confirm that loss of WRP is linked to impaired learning and memory.