Myosin-Va-interacting protein, RILPL2, controls cell shape and neuronal morphogenesis via Rac signaling

J Cell Sci. 2009 Oct 15;122(Pt 20):3810-21. doi: 10.1242/jcs.050344.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Brain / metabolism
  • COS Cells
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Shape*
  • Chlorocebus aethiops
  • Dendritic Spines / metabolism
  • Enzyme Activation
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Genes, Dominant
  • Hippocampus / metabolism
  • Mice
  • Morphogenesis*
  • Myosin Heavy Chains / metabolism*
  • Myosin Type V / metabolism*
  • Neurons / cytology*
  • Neurons / enzymology*
  • Organ Specificity
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Signal Transduction
  • Time Factors
  • rac GTP-Binding Proteins / metabolism*

Substances

  • Carrier Proteins
  • Myo5a protein, rat
  • RNA, Messenger
  • Myosin Type V
  • Myosin Heavy Chains
  • rac GTP-Binding Proteins