Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - The V0-ATPase mediates apical secretion of exosomes containing Hedgehog-related proteins in Caenorhabditis elegans
AU - Liégeois, Samuel
AU - Benedetto, Alexandre
AU - Garnier, Jean-Marie
AU - Schwab, Yannick
AU - Labouesse, Michel
PY - 2006/6/19
Y1 - 2006/6/19
N2 - 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.
AB - 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.
KW - Amino Acid Sequence
KW - Animals
KW - Caenorhabditis elegans
KW - Caenorhabditis elegans Proteins
KW - Hedgehog Proteins
KW - Models, Biological
KW - Molecular Sequence Data
KW - Mutagenesis, Site-Directed
KW - Phenotype
KW - Protein Structure, Tertiary
KW - Protein Transport
KW - Secretory Vesicles
KW - Sequence Alignment
KW - Trans-Activators
KW - Vacuolar Proton-Translocating ATPases
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1083/jcb.200511072
DO - 10.1083/jcb.200511072
M3 - Journal article
C2 - 16785323
VL - 173
SP - 949
EP - 961
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 6
ER -