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. 1996 Oct 29;93(22):12304–12308. doi: 10.1073/pnas.93.22.12304

Cytoplasm-to-vacuole targeting and autophagy employ the same machinery to deliver proteins to the yeast vacuole.

S V Scott 1, A Hefner-Gravink 1, K A Morano 1, T Noda 1, Y Ohsumi 1, D J Klionsky 1
PMCID: PMC37986  PMID: 8901576

Abstract

The vacuolar protein aminopeptidase I (API) uses a novel cytoplasm-to-vacuole targeting (Cvt) pathway. Complementation analysis of yeast mutants defective for cytoplasm-to-vacuole protein targeting (cvt) and autophagy (apg) revealed seven overlapping complementation groups between these two sets of mutants. In addition, all 14 apg complementation groups are defective in the delivery of API to the vacuole. Similarly, the majority of nonoverlapping cvt complementation groups appear to be at least partially defective in autophagy. Kinetic analyses of protein delivery rates indicate that autophagic protein uptake is induced by nitrogen starvation, whereas Cvt is a constitutive biosynthetic pathway. However, the machinery governing Cvt is affected by nitrogen starvation as targeting defects resulting from API overexpression can be rescued by induction of autophagy.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baba M., Osumi M., Ohsumi Y. Analysis of the membrane structures involved in autophagy in yeast by freeze-replica method. Cell Struct Funct. 1995 Dec;20(6):465–471. doi: 10.1247/csf.20.465. [DOI] [PubMed] [Google Scholar]
  2. Baba M., Takeshige K., Baba N., Ohsumi Y. Ultrastructural analysis of the autophagic process in yeast: detection of autophagosomes and their characterization. J Cell Biol. 1994 Mar;124(6):903–913. doi: 10.1083/jcb.124.6.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Conibear E., Stevens T. H. Vacuolar biogenesis in yeast: sorting out the sorting proteins. Cell. 1995 Nov 17;83(4):513–516. doi: 10.1016/0092-8674(95)90088-8. [DOI] [PubMed] [Google Scholar]
  4. Harding T. M., Hefner-Gravink A., Thumm M., Klionsky D. J. Genetic and phenotypic overlap between autophagy and the cytoplasm to vacuole protein targeting pathway. J Biol Chem. 1996 Jul 26;271(30):17621–17624. doi: 10.1074/jbc.271.30.17621. [DOI] [PubMed] [Google Scholar]
  5. Harding T. M., Morano K. A., Scott S. V., Klionsky D. J. Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway. J Cell Biol. 1995 Nov;131(3):591–602. doi: 10.1083/jcb.131.3.591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Klionsky D. J., Cueva R., Yaver D. S. Aminopeptidase I of Saccharomyces cerevisiae is localized to the vacuole independent of the secretory pathway. J Cell Biol. 1992 Oct;119(2):287–299. doi: 10.1083/jcb.119.2.287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Klionsky D. J., Emr S. D. Membrane protein sorting: biosynthesis, transport and processing of yeast vacuolar alkaline phosphatase. EMBO J. 1989 Aug;8(8):2241–2250. doi: 10.1002/j.1460-2075.1989.tb08348.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Klionsky D. J., Herman P. K., Emr S. D. The fungal vacuole: composition, function, and biogenesis. Microbiol Rev. 1990 Sep;54(3):266–292. doi: 10.1128/mr.54.3.266-292.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Klionsky D. J., Nelson H., Nelson N. Compartment acidification is required for efficient sorting of proteins to the vacuole in Saccharomyces cerevisiae. J Biol Chem. 1992 Feb 15;267(5):3416–3422. [PubMed] [Google Scholar]
  10. Morano K. A., Klionsky D. J. Differential effects of compartment deacidification on the targeting of membrane and soluble proteins to the vacuole in yeast. J Cell Sci. 1994 Oct;107(Pt 10):2813–2824. doi: 10.1242/jcs.107.10.2813. [DOI] [PubMed] [Google Scholar]
  11. Munn A. L., Riezman H. Endocytosis is required for the growth of vacuolar H(+)-ATPase-defective yeast: identification of six new END genes. J Cell Biol. 1994 Oct;127(2):373–386. doi: 10.1083/jcb.127.2.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Noda T., Matsuura A., Wada Y., Ohsumi Y. Novel system for monitoring autophagy in the yeast Saccharomyces cerevisiae. Biochem Biophys Res Commun. 1995 May 5;210(1):126–132. doi: 10.1006/bbrc.1995.1636. [DOI] [PubMed] [Google Scholar]
  13. Oda M. N., Scott S. V., Hefner-Gravink A., Caffarelli A. D., Klionsky D. J. Identification of a cytoplasm to vacuole targeting determinant in aminopeptidase I. J Cell Biol. 1996 Mar;132(6):999–1010. doi: 10.1083/jcb.132.6.999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Robinson J. S., Klionsky D. J., Banta L. M., Emr S. D. Protein sorting in Saccharomyces cerevisiae: isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases. Mol Cell Biol. 1988 Nov;8(11):4936–4948. doi: 10.1128/mcb.8.11.4936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Scott S. V., Klionsky D. J. In vitro reconstitution of cytoplasm to vacuole protein targeting in yeast. J Cell Biol. 1995 Dec;131(6 Pt 2):1727–1735. doi: 10.1083/jcb.131.6.1727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Stack J. H., Horazdovsky B., Emr S. D. Receptor-mediated protein sorting to the vacuole in yeast: roles for a protein kinase, a lipid kinase and GTP-binding proteins. Annu Rev Cell Dev Biol. 1995;11:1–33. doi: 10.1146/annurev.cb.11.110195.000245. [DOI] [PubMed] [Google Scholar]
  17. Takeshige K., Baba M., Tsuboi S., Noda T., Ohsumi Y. Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Biol. 1992 Oct;119(2):301–311. doi: 10.1083/jcb.119.2.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Teichert U., Mechler B., Müller H., Wolf D. H. Lysosomal (vacuolar) proteinases of yeast are essential catalysts for protein degradation, differentiation, and cell survival. J Biol Chem. 1989 Sep 25;264(27):16037–16045. [PubMed] [Google Scholar]
  19. Thumm M., Egner R., Koch B., Schlumpberger M., Straub M., Veenhuis M., Wolf D. H. Isolation of autophagocytosis mutants of Saccharomyces cerevisiae. FEBS Lett. 1994 Aug 1;349(2):275–280. doi: 10.1016/0014-5793(94)00672-5. [DOI] [PubMed] [Google Scholar]
  20. Tsukada M., Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993 Oct 25;333(1-2):169–174. doi: 10.1016/0014-5793(93)80398-e. [DOI] [PubMed] [Google Scholar]
  21. Umemoto N., Yoshihisa T., Hirata R., Anraku Y. Roles of the VMA3 gene product, subunit c of the vacuolar membrane H(+)-ATPase on vacuolar acidification and protein transport. A study with VMA3-disrupted mutants of Saccharomyces cerevisiae. J Biol Chem. 1990 Oct 25;265(30):18447–18453. [PubMed] [Google Scholar]
  22. van Weert A. W., Dunn K. W., Geuze H. J., Maxfield F. R., Stoorvogel W. Transport from late endosomes to lysosomes, but not sorting of integral membrane proteins in endosomes, depends on the vacuolar proton pump. J Cell Biol. 1995 Aug;130(4):821–834. doi: 10.1083/jcb.130.4.821. [DOI] [PMC free article] [PubMed] [Google Scholar]

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