TUC-4b, a novel TUC family variant, regulates neurite outgrowth and associates with vesicles in the growth cone

J Neurosci. 2003 Apr 1;23(7):2815-23. doi: 10.1523/JNEUROSCI.23-07-02815.2003.

Abstract

The TUC (TOAD-64/Ulip/CRMP) proteins are homologs of UNC-33, a protein that is required for axon extension and guidance in Caenorhabditis elegans. The TUC proteins are expressed in newly born neurons in the developing nervous system and have been implicated in semaphorin signaling and neuronal polarity. Here, we identify several new variants of the TUC family, each of which is expressed during distinct periods of neural development. We cloned and characterized TUC-4b, a variant of TUC-4a that includes a unique N-terminal extension. The functional relevance of this N-terminal domain is demonstrated by the finding that overexpression of TUC-4b, but not TUC-4a, results in increased neurite length and branching. Furthermore, whereas TUC-4a is expressed throughout life, TUC-4b is expressed exclusively during embryonic development. TUC-4b is localized to SV2 (synaptic vesicle protein 2)-positive vesicles in the central domain of the growth cone, suggesting a potential role in growth cone vesicle transport. Furthermore, TUC-4b interacts with the SH3A (Src homology 3A) domain of intersectin, an endocytic-exocytic adaptor protein. Together, these data suggest that TUC-4b can regulate neurite extension and branching through a mechanism that may involve membrane transport in the growth cone.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Vesicular Transport*
  • Amino Acid Sequence
  • Animals
  • Axons / physiology
  • Axons / ultrastructure
  • Caenorhabditis elegans Proteins / analysis*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Cloning, Molecular
  • Growth Cones / chemistry*
  • Molecular Sequence Data
  • Nerve Tissue Proteins / analysis*
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Nervous System / embryology
  • Nervous System / metabolism
  • Neurites / ultrastructure*
  • Protein Isoforms / analysis
  • Protein Isoforms / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Synaptic Vesicles / chemistry*
  • Synaptic Vesicles / physiology
  • src Homology Domains

Substances

  • Adaptor Proteins, Vesicular Transport
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Nerve Tissue Proteins
  • Protein Isoforms
  • intersectin 1

Associated data

  • GENBANK/AF398465