A novel phenylalanine-based targeting signal directs telencephalin to neuronal dendrites

J Neurosci. 2005 Feb 2;25(5):1122-31. doi: 10.1523/JNEUROSCI.3853-04.2005.

Abstract

Neurons sort out a variety of functional molecules to appropriate subcellular destinations. Telencephalin (TLCN; intercellular adhesion molecule-5) is a cell adhesion molecule specifically localized to somatodendritic membranes in the telencephalic neurons. Here, we established a new in vivo strategy to analyze neuronal sorting mechanisms by ectopic expression of molecules of interest in the cerebellar Purkinje cells of transgenic mice. By using this system, we identified a novel dendritic targeting determinant in the cytoplasmic tail region of TLCN. A full-length TLCN ectopically expressed in the Purkinje cells was localized exclusively to dendrites but not to axons. In contrast, a deletion of cytoplasmic C-terminal 12 amino acids (residues 901-912) or a point mutation of Phe905 to Ala abrogated the dendrite-specific targeting with appearance of the truncated and point-mutated TLCN in both axons and dendrites. Furthermore, an addition of the C-terminal 17 amino acids (residues 896-912) of TLCN to an unrelated molecule (CD8) was sufficient for its specific targeting to dendrites in several types of neurons. Because the C-terminal region of TLCN does not contain any canonical dendritic targeting sequences such as the tyrosine-based motif or the dileucine motif, this study suggests a novel mechanism of protein trafficking to the dendritic compartment of neurons.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Brain Chemistry
  • Cell Adhesion Molecules
  • Cell Membrane / metabolism*
  • Cell Polarity
  • Cells, Cultured / metabolism
  • Dendrites / metabolism*
  • Dogs
  • Epithelial Cells / cytology
  • Humans
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutation, Missense
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Phenylalanine / chemistry*
  • Point Mutation
  • Protein Sorting Signals / physiology*
  • Protein Structure, Tertiary
  • Protein Transport / physiology*
  • Purkinje Cells / metabolism*
  • Rabbits
  • Recombinant Fusion Proteins / analysis
  • Recombinant Fusion Proteins / physiology
  • Sequence Alignment
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Telencephalon / cytology

Substances

  • Cell Adhesion Molecules
  • ICAM5 protein, human
  • Icam5 protein, mouse
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Protein Sorting Signals
  • Recombinant Fusion Proteins
  • Phenylalanine