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Originally published In Press as doi:10.1074/jbc.M600927200 on April 18, 2006

J. Biol. Chem., Vol. 281, Issue 25, 17164-17172, June 23, 2006
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Alternative Splicing Controls Neuronal Expression of v-ATPase Subunit a1 and Sorting to Nerve Terminals*

Sandrine Poëa-Guyon, Muriel Amar, Philippe Fossier, and Nicolas Morel1

From the Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS UPR9040, 91198 Gif sur Yvette, France

Vacuolar proton ATPase accumulates protons inside various intracellular organelles such as synaptic vesicles; its membrane domain V0 could also be involved in membrane fusion. These different functions could require vacuolar proton ATPases possessing different V0 subunit a isoforms. In vertebrates, four genes encode isoforms a1–a4, and a1 variants are also generated by alternative splicing. We identified a novel a1 splice variant a1-IV and showed that the two a1 variants containing exon C are specifically expressed in neurons. Single neurons coexpress a2, a1-I, and a1-IV, and these subunit a isoforms are targeted to different membrane compartments. Recombinant a2 was accumulated in the trans-Golgi network, and a1-I was concentrated in axonal varicosities, whereas a1-IV was sorted to both distal dendrites and axons. Our results indicate that alternative splicing of exon N controls differential sorting of a1 variants to nerve terminals or distal dendrites, whereas exon C regulates their neuronal expression.


Received for publication, January 31, 2006 , and in revised form, March 9, 2006.

* This work was supported in part by Ministère délégué à la Recherche et aux Nouvelles Technologies Grant 04 2 425. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed. Tel.: 33-1-69823647; Fax: 33-1-69824141; E-mail: nicolas.morel{at}nbcm.cnrs-gif.fr.


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