V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway

Andrés Hurtado-Lorenzo, Mhairi Skinner, Jaafar El-Annan, Masamitsu Futai, Ge Hong Sun-Wada, Sylvain Bourgoin, James Casanova, Alan Wildeman, Shaliha Bechoua, Dennis A. Ausiello, Dennis Brown, Vladimir Marshansky

Research output: Contribution to journalArticle

319 Citations (Scopus)

Abstract

The recruitment of the small GTPase Arf6 and ARNO from cytosol to endosomal membranes is driven by V-ATPase-dependent intra-endosomal acidification. The molecular mechanism that mediates this pH-sensitive recruitment and its role are unknown. Here, we demonstrate that Arf6 interacts with the c-subunit, and ARNO with the a2-isoform of V-ATPase. The a2-isoform is targeted to early endosomes, interacts with ARNO in an intra-endosomal acidification-dependent manner, and disruption of this interaction results in reversible inhibition of endocytosis. Inhibition of endosomal acidification abrogates protein trafficking between early and late endosomal compartments. These data demonstrate the crucial role of early endosomal acidification and V-ATPase/ARNO/Arf6 interactions in the regulation of the endocytic degradative pathway. They also indicate that V-ATPase could modulate membrane trafficking by recruiting and interacting with ARNO and Arf6; characteristics that are consistent with the role of V-ATPase as an essential component of the endosomal pH-sensing machinery.

Original languageEnglish (US)
Pages (from-to)124-136
Number of pages13
JournalNature Cell Biology
Volume8
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

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Endosomes
Adenosine Triphosphatases
Proteins
Protein Isoforms
Membranes
Monomeric GTP-Binding Proteins
Protein Transport
Endocytosis
Cytosol

ASJC Scopus subject areas

  • Cell Biology

Cite this

Hurtado-Lorenzo, A., Skinner, M., El-Annan, J., Futai, M., Sun-Wada, G. H., Bourgoin, S., ... Marshansky, V. (2006). V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway. Nature Cell Biology, 8(2), 124-136. https://doi.org/10.1038/ncb1348

V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway. / Hurtado-Lorenzo, Andrés; Skinner, Mhairi; El-Annan, Jaafar; Futai, Masamitsu; Sun-Wada, Ge Hong; Bourgoin, Sylvain; Casanova, James; Wildeman, Alan; Bechoua, Shaliha; Ausiello, Dennis A.; Brown, Dennis; Marshansky, Vladimir.

In: Nature Cell Biology, Vol. 8, No. 2, 02.2006, p. 124-136.

Research output: Contribution to journalArticle

Hurtado-Lorenzo, A, Skinner, M, El-Annan, J, Futai, M, Sun-Wada, GH, Bourgoin, S, Casanova, J, Wildeman, A, Bechoua, S, Ausiello, DA, Brown, D & Marshansky, V 2006, 'V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway', Nature Cell Biology, vol. 8, no. 2, pp. 124-136. https://doi.org/10.1038/ncb1348
Hurtado-Lorenzo, Andrés ; Skinner, Mhairi ; El-Annan, Jaafar ; Futai, Masamitsu ; Sun-Wada, Ge Hong ; Bourgoin, Sylvain ; Casanova, James ; Wildeman, Alan ; Bechoua, Shaliha ; Ausiello, Dennis A. ; Brown, Dennis ; Marshansky, Vladimir. / V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway. In: Nature Cell Biology. 2006 ; Vol. 8, No. 2. pp. 124-136.
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