Abstract
Cilia are sensory organelles present on almost all vertebrate cells. Cilium length is constant, but varies between cell types, indicating that cilium length is regulated. How this is achieved is unclear, but protein transport in cilia (intraflagellar transport, IFT) plays an important role. Several studies indicate that cilium length and function can be modulated by environmental cues. As a model, we study a C. elegans mutant that carries a dominant active G protein α subunit (gpa-3QL), resulting in altered IFT and short cilia. In a screen for suppressors of the gpa-3QL short cilium phenotype, we identified uev-3, which encodes an E2 ubiquitin-conjugating enzyme variant that acts in a MAP kinase pathway. Mutation of two other components of this pathway, dual leucine zipper-bearing MAPKKK DLK-1 and p38 MAPK PMK-3, also suppress the gpa-3QL short cilium phenotype. However, this suppression seems not to be caused by changes in IFT. The DLK-1/p38 pathway regulates several processes, including microtubule stability and endocytosis. We found that reducing endocytosis by mutating rabx-5 or rme-6, RAB-5 GEFs, or the clathrin heavy chain, suppresses gpa-3QL. In addition, gpa-3QL animals showed reduced levels of two GFP-tagged proteins involved in endocytosis, RAB-5 and DPY-23, whereas pmk-3 mutant animals showed accumulation of GFP-tagged RAB-5. Together our results reveal a new role for the DLK-1/p38 MAPK pathway in control of cilium length by regulating RAB-5 mediated endocytosis.
Highlights
Primary cilia are evolutionarily conserved organelles that extend from the cell’s surface and are used to sense cues in the environment
Together our results reveal a new role for the DLK-1/p38 MAPK pathway in control of cilium length by regulating RAB-5 mediated endocytosis
Several genes have been identified that function in cilium length regulation and it is clear that transport of proteins inside the cilium plays an important role
Summary
Primary cilia are evolutionarily conserved organelles that extend from the cell’s surface and are used to sense cues in the environment. Cilia are present on most cells of the vertebrate body and harbor specific receptors and other signaling molecules depending on the cell type. All cilia contain a microtubule core, the axoneme. The axonemal microtubules are essential for a specialized transport pathway called intraflagellar transport (IFT) [2, 3]. IFT transports ciliary building blocks and signaling molecules along the axoneme to the ciliary tip (anterograde) and back to the base (retrograde). Anterograde transport is mediated by kinesin-2 and IFT dynein transports particles in the retrograde direction. In addition to the motors and cargo, IFT particles contain many other proteins, including complex A and complex B and Bardet-Biedl syndrome (BBS) proteins, that are thought to form a scaffold between cargo and motor complexes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
