Ciliary targeting of olfactory CNG channels requires the CNGB1b subunit and the kinesin-2 motor protein, KIF17

Curr Biol. 2006 Jun 20;16(12):1211-6. doi: 10.1016/j.cub.2006.04.034.

Abstract

Nonmotile cilia on olfactory sensory neurons (OSNs) compartmentalize signaling molecules, including odorant receptors and cyclic nucleotide-gated (CNG) channels, allowing for efficient, spatially confined responses to sensory stimuli . Little is known about the mechanisms of the ciliary targeting of olfactory CNG channels, composed of three subunits: CNGA2, CNGA4, and CNGB1b . Recent reports suggest that subunit composition of the retinal CNG channel influences localization, leading to disease . However, the mechanistic role of subunits in properly targeting native olfactory CNG channels remains unclear. Here, we show that heteromeric assembly with CNGB1b, containing a critical carboxy-terminal motif (RVxP), is required for ciliary trafficking of olfactory CNG channels. Movement of proteins within the cilia is governed by intraflagellar transport (IFT), a process that facilitates bidirectional movement of cargo along microtubules. Work in C. elegans has established that heterotrimeric and homodimeric kinesin-2 family members play a critical role in anterograde transport . In mammalian systems, the heterotrimeric KIF3a/KIF3b/KAP-3 complex plays a clear role in IFT; however, no role has been established for KIF17, the mammalian homolog of OSM-3 . Here, we demonstrate that KIF17 is required for olfactory CNG channel targeting, providing novel insights into mechanisms of mammalian ciliary transport.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cilia / metabolism*
  • Cilia / ultrastructure
  • Cyclic Nucleotide-Gated Cation Channels
  • Dogs
  • Ion Channels / chemistry
  • Ion Channels / metabolism*
  • Kinesin / metabolism*
  • Luminescent Proteins / analysis
  • Molecular Motor Proteins / metabolism*
  • Molecular Sequence Data
  • Protein Subunits / metabolism*
  • Protein Transport
  • Sequence Alignment

Substances

  • Cyclic Nucleotide-Gated Cation Channels
  • Ion Channels
  • Luminescent Proteins
  • Molecular Motor Proteins
  • Protein Subunits
  • Kinesin