| RRC ID |
88138
|
| Author |
Wang S, Li M, Chen G, Chen Z, Lei K, Ökten Z, Xie S, Zhou T, Li W, Ou G.
|
| Title |
Joubert syndrome 26 protein enforces compartmentalized motility of a ciliary kinesin.
|
| Journal |
Proc Natl Acad Sci U S A
|
| Abstract |
Cilia are essential cellular antennae that rely on precise motor-driven transport to assemble and function. Two kinesin-2 motors-kinesin-II and OSM-3 in Caenorhabditis elegans-cooperate to transport cargo along cilia, with kinesin-II operating in the middle segment and OSM-3 taking over distally. However, how kinesin-II is spatially confined to prevent its invasion into distal regions remains unclear. Here, we identify Joubert syndrome 26 protein (JBTS-26) as a critical regulator of this motor handover. JBTS-26 localizes to axonemal doublet microtubules in the ciliary middle segment, where it competes with kinesin-II for binding to the IFT-B subunit OSM-5/IFT88. This competition displaces kinesin-II from IFT particles, enabling OSM-3 to assume distal transport. Loss of JBTS-26 allows kinesin-II to invade the distal cilium and slows down IFT. Conversely, JBTS-26 overexpression accelerates IFT by prematurely releasing kinesin-II. Our findings reveal a mechanism for compartmentalized motor regulation and link defective motor handover to ciliopathy pathogenesis.
|
| Volume |
122(47)
|
| Pages |
e2504374122
|
| Published |
2025-11-25
|
| DOI |
10.1073/pnas.2504374122
|
| PMID |
41264249
|
| PMC |
PMC12663925
|
| MeSH |
Abnormalities, Multiple
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
Cerebellum / abnormalities
Cerebellum / metabolism
Cilia* / metabolism
Eye Abnormalities* / genetics
Eye Abnormalities* / metabolism
Humans
Kidney Diseases, Cystic* / genetics
Kidney Diseases, Cystic* / metabolism
Kinesins* / genetics
Kinesins* / metabolism
Microtubules / metabolism
Retina* / abnormalities
Retina* / metabolism
|
| Resource |
| C.elegans |
tm324 |
