The AP-1 clathrin adaptor facilitates cilium formation and functions with RAB-8 in C. elegans ciliary membrane transport.
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.
Kaplan
Oktay I
OI
School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Molla-Herman
Anahi
A
Cevik
Sebiha
S
Ghossoub
Rania
R
Kida
Katarzyna
K
Kimura
Yoshishige
Y
Jenkins
Paul
P
Martens
Jeffrey R
JR
Setou
Mitsutoshi
M
Benmerah
Alexandre
A
Blacque
Oliver E
OE
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
D033961:Adaptor Protein Complex 1; D002966:Clathrin