The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase

Dev Cell. 2008 Feb;14(2):216-26. doi: 10.1016/j.devcel.2007.11.020.

Abstract

The majority of excitatory synaptic transmission in the brain occurs at dendritic spines, which are actin-rich protrusions on the dendrites. The asymmetric nature of these structures suggests that proteins regulating cell polarity might be involved in their formation. Indeed, the polarity protein PAR-3 is required for normal spine morphogenesis. However, this function is independent of association with atypical protein kinase C (aPKC) and PAR-6. Here we show that PAR-6 together with aPKC plays a distinct but essential role in spine morphogenesis. Knockdown of PAR-6 inhibits spine morphogenesis, whereas overexpression of PAR-6 increases spine density, and these effects are mediated by aPKC. Using a FRET biosensor, we further show that p190 RhoGAP and RhoA act downstream of the PAR-6/aPKC complex. These results define a role for PAR-6 and aPKC in dendritic spine biogenesis and maintenance, and reveal an unexpected link between the PAR-6/aPKC complex and RhoA activity.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Carrier Proteins / metabolism*
  • Cell Polarity*
  • DNA-Binding Proteins / metabolism*
  • Dendritic Spines / enzymology*
  • Morphogenesis*
  • Mutation / genetics
  • Protein Kinase C / metabolism
  • Rats
  • Repressor Proteins / metabolism*
  • rho GTP-Binding Proteins / metabolism*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Arhgap35 protein, rat
  • Carrier Proteins
  • DNA-Binding Proteins
  • Pard6a protein, rat
  • Repressor Proteins
  • protein kinase C zeta
  • PKC-3 protein
  • Protein Kinase C
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein