title: The AP-1 clathrin adaptor facilitates cilium formation and functions with RAB-8 in C. elegans ciliary membrane transport.
abstract: Clathrin adaptor (AP) complexes facilitate membrane trafficking between subcellular compartments. One such compartment is the cilium, whose dysfunction underlies disorders classified as ciliopathies. Although AP-1mu subunit (UNC-101) is linked to cilium formation and targeting of transmembrane proteins (ODR-10) to nematode sensory cilia at distal dendrite tips, these functions remain poorly understood. Here, using Caenorhabditis elegans sensory neurons and mammalian cell culture models, we find conservation of AP-1 function in facilitating cilium morphology, positioning and orientation, and microtubule stability and acetylation. These defects appear to be independent of IFT, because AP-1-depleted cells possess normal IFT protein localisation and motility. By contrast, disruption of chc-1 (clathrin) or rab-8 phenocopies unc-101 worms, preventing ODR-10 vesicle formation and causing misrouting of ODR-10 to all plasma membrane destinations. Finally, ODR-10 colocalises with RAB-8 in cell soma and they cotranslocate along dendrites, whereas ODR-10 and UNC-101 signals do not overlap. Together, these data implicate conserved roles for metazoan AP-1 in facilitating cilium structure and function, and suggest cooperation with RAB-8 to coordinate distinct early steps in neuronal ciliary membrane sorting and trafficking.
authors.affiliation: School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Oktay I
authors.initials: OI
authors.lastname: Kaplan
authors.forename: Anahi
authors.initials: A
authors.lastname: Molla-Herman
authors.forename: Sebiha
authors.initials: S
authors.lastname: Cevik
authors.forename: Rania
authors.initials: R
authors.lastname: Ghossoub
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kida
authors.forename: Yoshishige
authors.initials: Y
authors.lastname: Kimura
authors.forename: Paul
authors.initials: P
authors.lastname: Jenkins
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Martens
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
authors.forename: Alexandre
authors.initials: A
authors.lastname: Benmerah
authors.forename: Oliver E
authors.initials: OE
authors.lastname: Blacque
mesh_terms: D033961:Adaptor Protein Complex 1 / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002923:Cilia / Q000378:metabolism / Q000648:ultrastructure; D002966:Clathrin / Q000378:metabolism
chemical_list: D033961:Adaptor Protein Complex 1; D002966:Clathrin