Involvement of Girdin in the determination of cell polarity during cell migration

PLoS One. 2012;7(5):e36681. doi: 10.1371/journal.pone.0036681. Epub 2012 May 4.

Abstract

Cell migration is a critical cellular process that determines embryonic development and the progression of human diseases. Therefore, cell- or context-specific mechanisms by which multiple promigratory proteins differentially regulate cell migration must be analyzed in detail. Girdin (girders of actin filaments) (also termed GIV, Gα-interacting vesicle associated protein) is an actin-binding protein that regulates migration of various cells such as endothelial cells, smooth muscle cells, neuroblasts, and cancer cells. Here we show that Girdin regulates the establishment of cell polarity, the deregulation of which may result in the disruption of directional cell migration. We found that Girdin interacts with Par-3, a scaffolding protein that is a component of the Par protein complex that has an established role in determining cell polarity. RNA interference-mediated depletion of Girdin leads to impaired polarization of fibroblasts and mammary epithelial cells in a way similar to that observed in Par-3-depleted cells. Accordingly, the expression of Par-3 mutants unable to interact with Girdin abrogates cell polarization in fibroblasts. Further biochemical analysis suggests that Girdin is present in the Par protein complex that includes Par-3, Par-6, and atypical protein kinase C. Considering previous reports showing the role of Girdin in the directional migration of neuroblasts, network formation of endothelial cells, and cancer invasion, these data may provide a specific mechanism by which Girdin regulates cell movement in biological contexts that require directional cell movement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism
  • Cell Division
  • Cell Line
  • Cell Movement*
  • Cell Polarity*
  • Cytoplasm / metabolism
  • Down-Regulation
  • Fibroblasts / cytology
  • Gene Knockout Techniques
  • Humans
  • Mammary Glands, Human / cytology
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Mice
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / deficiency
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Neurons / cytology
  • Protein Structure, Tertiary
  • Vesicular Transport Proteins / chemistry
  • Vesicular Transport Proteins / deficiency
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*

Substances

  • CCDC88A protein, human
  • Cell Cycle Proteins
  • Membrane Proteins
  • Microfilament Proteins
  • PARD3 protein, human
  • Vesicular Transport Proteins
  • girdin protein, mouse