Ciliary targeting of olfactory CNG channels requires the CNGB1b subunit and the kinesin-2 motor protein, KIF17.
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.
Jenkins
Paul M
PM
Department of Pharmacology, University of Michigan, Ann Arbor, 48109, USA.
Hurd
Toby W
TW
Zhang
Lian
L
McEwen
Dyke P
DP
Brown
R Lane
RL
Margolis
Ben
B
Verhey
Kristen J
KJ
Martens
Jeffrey R
JR
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D054815:Cyclic Nucleotide-Gated Cation Channels; D004285:Dogs; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D016547:Kinesins / Q000378:metabolism*; D008164:Luminescent Proteins / Q000032:analysis; D020409:Molecular Motor Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D021122:Protein Subunits / Q000378:metabolism*; D021381:Protein Transport; D016415:Sequence Alignment
D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; D008164:Luminescent Proteins; D020409:Molecular Motor Proteins; D021122:Protein Subunits; D016547:Kinesins