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

Marie France Lisé*, Deepak P. Srivastava, Pamela Arstikaitis, Robyn L. Lett, Razan Sheta, Vijay Viswanathan, Peter Penzes, Timothy P. O'Connor, Alaa El-Husseini

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3810-3821
Number of pages12
JournalJournal of cell science
Volume122
Issue number20
DOIs
StatePublished - Oct 15 2009

Keywords

  • Actin
  • Dendritic spine
  • Myosin-V
  • RILPL2
  • Rac1

ASJC Scopus subject areas

  • Cell Biology

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