The V0-ATPase mediates apical secretion of exosomes containing Hedgehog-related proteins in Caenorhabditis elegans.
Polarized intracellular trafficking in epithelia is critical in development, immunity, and physiology to deliver morphogens, defensins, or ion pumps to the appropriate membrane domain. The mechanisms that control apical trafficking remain poorly defined. Using Caenorhabditis elegans, we characterize a novel apical secretion pathway involving multivesicularbodies and the release of exosomes at the apical plasma membrane. By means of two different genetic approaches, we show that the membrane-bound V0 sector of the vacuolar H+-ATPase (V-ATPase) acts in this pathway, independent of its contribution to the V-ATPase proton pump activity. Specifically, we identified mutations in the V0 "a" subunit VHA-5 that affect either the V0-specific function or the V0+V1 function of the V-ATPase. These mutations allowed us to establish that the V0 sector mediates secretion of Hedgehog-related proteins. Our data raise the possibility that the V0 sector mediates exosome and morphogen release in mammals.
Liégeois
Samuel
S
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Universite Louis Pasteur, 67400 Illkirch, France.
Benedetto
Alexandre
A
Garnier
Jean-Marie
JM
Schwab
Yannick
Y
Labouesse
Michel
M
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053823:Hedgehog Proteins; D008954:Models, Biological; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D022142:Secretory Vesicles / Q000502:physiology* / Q000648:ultrastructure; D016415:Sequence Alignment; D015534:Trans-Activators / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D053823:Hedgehog Proteins; D015534:Trans-Activators; C512430:VHA-5 protein, C elegans; D025262:Vacuolar Proton-Translocating ATPases