The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesis

Nat Cell Biol. 2006 Mar;8(3):227-37. doi: 10.1038/ncb1368. Epub 2006 Feb 12.

Abstract

PAR-3 (partitioning-defective gene 3) is essential for cell polarization in many contexts, including axon specification. However, polarity proteins have not been implicated in later steps of neuronal differentiation, such as dendritic spine morphogenesis. Here, we show that PAR-3 is necessary for normal spine development in primary hippocampal neurons. Depletion of PAR-3 causes the formation of multiple filopodia- and lamellipodia-like dendritic protrusions - a phenotype similar to neurons expressing activated Rac. PAR-3 regulates spine formation by binding the Rac guanine nucleotide-exchange factor (GEF) TIAM1, and spatially restricting it to dendritic spines. Thus, a balance of PAR-3 and TIAM1 is essential to modulate Rac-GTP levels and to allow spine morphogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cell Differentiation
  • Cell Polarity
  • Cells, Cultured
  • Dendritic Spines / metabolism
  • Dendritic Spines / physiology*
  • Dendritic Spines / ultrastructure
  • Embryo, Mammalian / cytology
  • Guanine Nucleotide Exchange Factors / metabolism
  • Guanine Nucleotide Exchange Factors / physiology*
  • Hippocampus / cytology
  • Morphogenesis*
  • Neoplasm Proteins / metabolism
  • Neoplasm Proteins / physiology*
  • Nerve Tissue Proteins
  • Pseudopodia / ultrastructure
  • Rats
  • Synapsins / metabolism
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1
  • rac GTP-Binding Proteins / metabolism

Substances

  • Carrier Proteins
  • Guanine Nucleotide Exchange Factors
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Pard3 protein, rat
  • Synapsins
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1
  • Tiam1 protein, rat
  • rac GTP-Binding Proteins