Specific sorting of the a1 isoform of the V-H+ATPase a subunit to nerve terminals where it associates with both synaptic vesicles and the presynaptic plasma membrane.
Vacuolar H+ATPase (V-ATPase) accumulates protons inside various intracellular organelles, generating the electrochemical proton gradient required for many vital cellular processes. V-ATPase is a complex enzyme with many subunits that are organized into two domains. The membrane domain that translocates protons contains a proteolipid oligomer of several c subunits and a 100 kDa a subunit. Several a-subunit isoforms have been described that are important for tissue specificity and targeting to different membrane compartments, and could also result in the generation of V-ATPases with different functional properties. In the present report, we have cloned the Torpedo marmorata a1 isoform. This isoform was found to be addressed specifically to nerve endings, whereas VATPases in the neuron cell bodies contain a different a-subunit isoform. In nerve terminals, the V-ATPase membrane domain is present not only in synaptic vesicles but also in the presynaptic plasma membrane, where its density could reach 200 molecules microm(-2). This V-ATPase interacts with VAMP-2 and with the SNARE complexes involved in synaptic vesicle docking and exocytosis.
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, 91198 Gif sur Yvette, France. nicolas.morel@nbcm.cnrs-gif.fr
Nicolas
N
Morel
Jean-Claude
JC
Dedieu
Jean-Marc
JM
Philippe
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D003001:Cloning, Molecular; D020285:Cryoelectron Microscopy; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009411:Nerve Endings / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology*; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D013574:Synaptosomes / Q000378:metabolism*; D014101:Torpedo / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*; D033921:Vesicular Transport Proteins
D008565:Membrane Proteins; D020033:Protein Isoforms; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D025262:Vacuolar Proton-Translocating ATPases