Regulation of neuronal morphology by Toca-1, an F-BAR/EFC protein that induces plasma membrane invagination

J Biol Chem. 2006 Sep 29;281(39):29042-53. doi: 10.1074/jbc.M604025200. Epub 2006 Aug 2.

Abstract

Actin reorganization is important for regulation of neuronal morphology. Neural Wiskott-Aldrich syndrome protein (N-WASP) is an important regulator of actin polymerization and also known to be strongly expressed in brain. Recently, Toca-1 (transducer of Cdc42-dependent actin assembly) has been shown to be required for Cdc42 to activate N-WASP from biochemical experiments. Toca-1 has three functional domains: an F-BAR/EFC domain at the N terminus, an HR1 at the center, and an SH3 domain at the C terminus. The F-BAR/EFC domain induces tubular invagination of plasma membrane, while Toca-1 binds both N-WASP and Cdc42 through the SH3 domain and the HR1, respectively. However, the physiological role of Toca-1 is completely unknown. Here we have investigated the neural function of Toca-1. Toca-1 is strongly expressed in neurons including hippocampal neurons in developing brain at early times. Knockdown of Toca-1 in PC12 cells significantly enhances neurite elongation. Consistently, overexpression of Toca-1 suppresses neurite elongation through the F-BAR/EFC domain with a membrane invaginating property, suggesting an implication of membrane trafficking in the neural function of Toca-1. In addition, knockdown of N-WASP, to our surprise, also enhances neurite elongation in PC12 cells, which is in clear contrast to the previous report that dominant negative mutants of N-WASP suppress neurite extension in PC12 cells. On the other hand, knockdown of Toca-1 in cultured rat hippocampal neurons enhances axon branching a little but not axon elongation, while knockdown of N-WASP enhances both axon elongation and branching. These results suggest that a vesicle trafficking regulator Toca-1 regulates different aspects of neuronal morphology from N-WASP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / chemistry
  • Adaptor Proteins, Vesicular Transport / physiology*
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cell Membrane / metabolism*
  • HeLa Cells
  • Hippocampus / metabolism
  • Humans
  • Molecular Sequence Data
  • Neurons / metabolism
  • PC12 Cells
  • Rats
  • Wiskott-Aldrich Syndrome Protein, Neuronal / metabolism
  • cdc42 GTP-Binding Protein / metabolism

Substances

  • Adaptor Proteins, Vesicular Transport
  • Carrier Proteins
  • FNBP1L protein, human
  • Fnbp1l protein, rat
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • cdc42 GTP-Binding Protein

Associated data

  • GENBANK/AB250295
  • GENBANK/AB250296