Myosin-Va-interacting protein, RILPL2, controls cell shape and neuronal morphogenesis via Rac signaling.
ABSTRACT 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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ABSTRACT: The actin cytoskeleton plays a fundamental role in all eukaryotic cells it is a major determinant of cell morphology and polarity and the assembly and disassembly of filamentous actin structures provides a driving force for dynamic processes such as cell motility, phagocytosis, growth cone guidance and cytokinesis. The ability to reorganize actin filaments is a fundamental property of embryonic cells during development; the shape changes accompanying gastrulation and dorsal closure, for example, are dependent on the plasticity of the actin cytoskeleton, while the ability of cells or cell extensions, such as axons, to migrate within the developing embryo requires rapid and spatially organized changes to the actin cytoskeleton in response to the external environment. Work in mammalian cells over the last decade has demonstrated the central role played by the highly conserved Rho family of small GTPases in signal transduction pathways that link plasma membrane receptors to the organization of the actin cytoskeleton.Philosophical Transactions of The Royal Society B Biological Sciences 08/2000; 355(1399):965-70. · 6.23 Impact Factor
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ABSTRACT: Dendrite structures exert a profound influence on neuronal information processing. The Rho family GTPases have been implicated in the regulation of dendritic development. Among them, Rho, Rac, and Cdc42 have been characterized extensively, and Rac and Cdc42 promote dendrite growth and branching, whereas Rho acts as a negative regulator for dendrite growth. Recently, other members of Rho family GTPases, including Rnd1 and Rnd2, have also been shown to be involved in the regulation of dendrite development. Rnd1 promotes spine maturation, and Rnd2 stimulates dendrite branching through its specific effector, Rapostlin. Thus, a variety of Rho family GTPases play important roles in dendritic development.The Neuroscientist 07/2005; 11(3):187-91. · 5.63 Impact Factor
- Annual Review of Neuroscience 02/1994; 17:341-71. · 20.61 Impact Factor