Identification and characterization of Slitrk, a novel neuronal transmembrane protein family controlling neurite outgrowth

Mol Cell Neurosci. 2003 Sep;24(1):117-29. doi: 10.1016/s1044-7431(03)00129-5.

Abstract

The Slitrk family consists of six structurally related transmembrane proteins (Slitrk1-6) in the mouse. In the extracellular region, they share two conserved leucine-rich repeat domains that have a significant homology to a secreted axonal growth-controlling protein, Slit. These proteins also have a homology to trk neurotrophin receptors in their intracellular domains, sharing a conserved tyrosine residue. Expression of Slitrk is highly restricted to neural tissues, but varies within the family. More specifically, Slitrk1 expression is in the mature neurons, whereas Slitrk2 is strongly expressed in the ventricular layer, and Slitrk6 shows compartmentalized expression in diencephalon. Over-expressed Slitrk1 induced unipolar neurites in cultured neuronal cells, whereas Slitrk2 and other Slitrk proteins inhibited neurite outgrowth. Deletion analysis showed that the functional difference between Slitrk1 and Slitrk2 lies in their intracellular domains, which are conserved in Slitrk2-6, but not in Slitrk1. These results suggest that the Slitrk proteins are the neuronal components that control the neurite outgrowth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Base Sequence / genetics
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Central Nervous System / cytology
  • Central Nervous System / embryology
  • Central Nervous System / metabolism*
  • DNA, Complementary / analysis
  • DNA, Complementary / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / isolation & purification*
  • Membrane Proteins / pharmacology
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / isolation & purification*
  • Nerve Tissue Proteins / pharmacology
  • Neurites / drug effects
  • Neurites / metabolism*
  • Neurites / ultrastructure
  • PC12 Cells
  • Protein Isoforms / genetics
  • Protein Isoforms / isolation & purification
  • Protein Isoforms / pharmacology
  • Protein Structure, Tertiary / physiology
  • Rats
  • Receptor, trkA / metabolism

Substances

  • DNA, Complementary
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Protein Isoforms
  • SLITRK1 protein, mouse
  • Slitrk protein, mouse
  • Receptor, trkA

Associated data

  • GENBANK/AB097570
  • GENBANK/AB097571
  • GENBANK/AB097572
  • GENBANK/AB097573
  • GENBANK/AB097574
  • GENBANK/AB097575