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Originally published as MBC in Press, 10.1091/mbc.E06-08-0664 on November 1, 2006

Vol. 18, Issue 1, 166-175, January 2007

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The Vacuolar Transporter Chaperone (VTC) Complex Is Required for Microautophagy

Andreas Uttenweiler*, Heinz Schwarz{dagger}, Heinz Neumann*, and Andreas Mayer*

*Département de Biochimie, Université de Lausanne, 1066 Epalinges, Switzerland; and {dagger}Max-Planck-Institut für Entwicklungsbiologie, 72076 Tübingen, Germany

Submitted August 2, 2006; Revised October 10, 2006; Accepted October 20, 2006
Monitoring Editor: Howard Riezman

Microautophagy involves direct invagination and fission of the vacuolar/lysosomal membrane under nutrient limitation. This occurs by an autophagic tube, a specialized vacuolar membrane invagination that pinches off vesicles into the vacuolar lumen. In this study we have identified the VTC (vacuolar transporter chaperone) complex as required for microautophagy. The VTC complex is present on the ER and vacuoles and at the cell periphery. On induction of autophagy by nutrient limitation the VTC complex is recruited to and concentrated on vacuoles. The VTC complex is inhomogeneously distributed within the vacuolar membranes, showing an enrichment on autophagic tubes. Deletion of the VTC complex blocks microautophagic uptake into vacuoles. The mutants still form autophagic tubes but the production of microautophagic vesicles from their tips is impaired. In line with this, affinity-purified antibodies to the Vtc proteins inhibit microautophagic uptake in a reconstituted system in vitro. Our data suggest that the VTC complex is an important constituent of autophagic tubes and that it is required for scission of microautophagic vesicles from these tubes.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-08-0664) on November 1, 2006.

Address correspondence to: Andreas Mayer (andreas.mayer{at}unil.ch)

Abbreviations used: Cmd1, calmodulin; VTC, vacuolar transporter chaperone.




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