A role for nyctalopin, a small leucine-rich repeat protein, in localizing the TRP melastatin 1 channel to retinal depolarizing bipolar cell dendrites

J Neurosci. 2011 Jul 6;31(27):10060-6. doi: 10.1523/JNEUROSCI.1014-11.2011.

Abstract

Expression of channels to specific neuronal sites can critically impact their function and regulation. Currently, the molecular mechanisms underlying this targeting and intracellular trafficking of transient receptor potential (TRP) channels remain poorly understood, and identifying proteins involved in these processes will provide insight into underlying mechanisms. Vision is dependent on the normal function of retinal depolarizing bipolar cells (DBCs), which couple a metabotropic glutamate receptor 6 to the TRP melastatin 1 (TRPM1) channel to transmit signals from photoreceptors. We report that the extracellular membrane-attached protein nyctalopin is required for the normal expression of TRPM1 on the dendrites of DBCs in mus musculus. Biochemical and genetic data indicate that nyctalopin and TRPM1 interact directly, suggesting that nyctalopin is acting as an accessory TRP channel subunit critical for proper channel localization to the synapse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / pharmacology
  • Animals
  • Bacterial Proteins / genetics
  • Biophysics
  • Cell Line, Transformed
  • Dendrites / metabolism*
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / genetics*
  • Humans
  • In Vitro Techniques
  • Luminescent Proteins / genetics
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Biological
  • Patch-Clamp Techniques
  • Proteins / genetics
  • Proteins / metabolism*
  • Proteoglycans / genetics
  • Proteoglycans / metabolism
  • Retina / cytology*
  • Retina / growth & development
  • Retinal Bipolar Cells / cytology*
  • TRPM Cation Channels / deficiency
  • TRPM Cation Channels / metabolism*
  • Transfection / methods
  • Xanthenes / pharmacology

Substances

  • Amino Acids
  • Bacterial Proteins
  • Excitatory Amino Acid Antagonists
  • LY 341495
  • Luminescent Proteins
  • Proteins
  • Proteoglycans
  • TRPM Cation Channels
  • Trpm1 protein, mouse
  • Xanthenes
  • leucine-rich repeat proteins
  • nyctalopin protein, mouse
  • yellow fluorescent protein, Bacteria