unc-44 Ankyrin and stn-2 gamma-syntrophin regulate sax-7 L1CAM function in maintaining neuronal positioning in Caenorhabditis elegans

Genetics. 2008 Nov;180(3):1429-43. doi: 10.1534/genetics.108.091272. Epub 2008 Sep 14.

Abstract

The L1 family of single-pass transmembrane cell adhesion molecules (L1CAMs) is conserved from Caenorhabditis elegans and Drosophila to vertebrates and is required for axon guidance, neurite outgrowth, and maintenance of neuronal positions. The extracellular region of L1CAMs mediates cell adhesion via interactions with diverse cell-surface and extracellular matrix proteins. In contrast, less is known regarding the function of the intracellular domains in the L1CAM cytoplasmic tail. Previously, we identified a role of the C. elegans L1CAM homolog, SAX-7, in maintaining neuronal and axonal positioning. Here, we demonstrate that this function is dependent on three conserved motifs that reside in the SAX-7 cytoplasmic tail: (1) the FERM-binding motif, (2) the ankyrin-binding domain, and (3) the PDZ-binding motif. Furthermore, we provide molecular and genetic evidence that UNC-44 ankyrin and STN-2 gamma-syntrophin bind SAX-7 via the respective ankyrin-binding and PDZ-binding motifs to regulate SAX-7 function in maintaining neuronal positioning.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Ankyrins / genetics
  • Ankyrins / metabolism*
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / physiology*
  • Cells, Cultured
  • Fluorescent Antibody Technique
  • Humans
  • Kidney / metabolism
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Muscle, Striated / physiology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neural Cell Adhesion Molecule L1 / physiology*
  • Neural Cell Adhesion Molecules / genetics*
  • Neural Cell Adhesion Molecules / metabolism
  • Neurons / cytology
  • Neurons / physiology*
  • Phenotype
  • Sarcomeres / physiology
  • Two-Hybrid System Techniques

Substances

  • Ankyrins
  • Caenorhabditis elegans Proteins
  • Muscle Proteins
  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecule L1
  • Neural Cell Adhesion Molecules
  • SAX-7 protein, C elegans
  • stn-1 protein, C elegans
  • unc-44 protein, C elegans