生物
细胞生物学
RAC1
小发夹RNA
肌球蛋白
树突棘
肌动蛋白
形态发生
基因敲除
肌动蛋白细胞骨架
细胞骨架
GTP酶
RNA干扰
小型GTPase
Rac-GTP结合蛋白
信号转导
细胞
神经科学
核糖核酸
海马结构
细胞培养
基因
生物化学
遗传学
作者
Marie-France Lisé,Deepak P. Srivastava,Pamela Arstikaitis,Robyn L. M. Lett,Razan Sheta,Vijay Viswanathan,Peter Penzes,Timothy P. O’Connor,Alaa El-Husseini
摘要
Neuronal morphology plays an essential role in neuronal function. The establishment and maintenance of neuronal morphology is intimately linked to the actin cytoskeleton; however, the molecular mechanisms that regulate changes in neuronal morphology are poorly understood. Here we identify a novel myosin-Va (MyoVa)-interacting protein, RILPL2, which regulates cellular morphology. Overexpression of this protein in young or mature hippocampal neurons results in an increase in the number of spine-like protrusions. By contrast, knockdown of endogenous RILPL2 in neurons by short hairpin RNA (shRNA) interference results in reduced spine-like protrusions, a phenotype rescued by overexpression of an shRNA-insensitive RILPL2 mutant, suggesting a role for RILPL2 in both the establishment and maintenance of dendritic spines. Interestingly, we demonstrate that RILPL2 and the Rho GTPase Rac1 form a complex, and that RILPL2 is able to induce activation of Rac1 and its target, p21-activated kinase (Pak). Notably, both RILPL2-mediated morphological changes and activation of Rac1-Pak signaling were blocked by expression of a truncated tail form of MyoVa or MyoVa shRNA, demonstrating that MyoVa is crucial for proper RILPL2 function. This might represent a novel mechanism linking RILPL2, the motor protein MyoVa and Rac1 with neuronal structure and function.
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