The hydrolethalus syndrome protein HYLS-1 regulates formation of the ciliary gate

Abstract

Transition fibres (TFs), together with the transition zone (TZ), are basal ciliary structures thought to be crucial for cilium biogenesis and function by acting as a ciliary gate to regulate selective protein entry and exit. Here we demonstrate that the centriolar and basal body protein HYLS-1, the C. elegans orthologue of hydrolethalus syndrome protein 1, is required for TF formation, TZ organization and ciliary gating. Loss of HYLS-1 compromises the docking and entry of intraflagellar transport (IFT) particles, ciliary gating for both membrane and soluble proteins, and axoneme assembly. Additional depletion of the TF component DYF-19 in hyls-1 mutants further exacerbates TZ anomalies and completely abrogates ciliogenesis. Our data support an important role for HYLS-1 and TFs in establishment of the ciliary gate and underline the importance of selective protein entry for cilia assembly.

Centriole translocation and degeneration during ciliogenesis in Caenorhabditis elegans neurons

“…Axonemal microtubules are invariably organized in a radial ninefold symmetry, which is thought to originate from the nine spokes in the cartwheel. Centriole satellites are essential for ciliogenesis (Anderson, ; Vorobjev & Chentsov Yu, ; Tanos et al , ; Tateishi et al , ); the C. elegans homolog of hydrolethalus syndrome protein 1 (HYLS‐1) is required for anchoring of centrioles at the plasma membrane in sensory neurons (Dammermann et al , ; Wei et al , ). HYLS‐1 marks the centriolar MTs that spread out at the base of worm cilia, presumably due to the loss of the central tube (Dammermann et al , ; Doroquez et al , ).…”

Primary Cilium Formation and Ciliary Protein Trafficking Is Regulated by the Atypical MAP Kinase MAPK15 inCaenorhabditis elegansand Human Cells

“…We examined MAPK-15 distribution in loss-of-function alleles of IFT (osm-5/IFT88, che-11/ IFT140, xbx-1/DLIC, klp-11/KIF3B, and osm-3/KIF17) and BBSome (bbs-8/BBS8) genes. We also investigated MAPK-15 localization in hyls-1 and dyf-5 mutants: HYLS-1 (Hydrolethalus syndrome protein 1) at the basal body regulates the formation of the transition fibers that dock IFT assemblies, and DYF-5 (MAK ortholog) is a MAP kinase-related protein that regulates kinesin-2 IFT motors (Burghoorn et al 2007;Mohan et al 2013;Wei et al 2016). MAPK-15 retains grossly normal localization in most examined mutants despite the ciliary structural defects observed in many of these strains ( Figure S3 in File S1).…”

“…the basal body and the proximal-most region of the axoneme (transition zone). For instance, ciliopathy-associated proteins facilitate diffusion barriers at the transition zone, and basal body distal appendage components regulate IFT/BBSome protein entry into cilia (Craige et al 2010;Chih et al 2011;Garcia-Gonzalo et al 2011;Williams et al 2011;Wei et al 2013Wei et al , 2016Garcia-Gonzalo and Reiter 2016).…”

Rpgrip1l controls ciliary gating by ensuring the proper amount of Cep290 at the vertebrate transition zone

“…For this reason, the assembly and function of the TZ is a hot topic in biomedical research. A lot of proteins participate in TZ assembly and/or function as ciliary gatekeepers at the TZ [12- 14,16,17,19,23,24,27,29,30,33,34,37,41,69,70,[73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90]. However, the relationships between these proteins and hence the mechanisms underlying ciliary gating at the TZ remain largely elusive.…”