Cargando…

Two Distinct Pathways for Targeting Proteins from the Cytoplasm to the Vacuole/Lysosome

Stress conditions lead to a variety of physiological responses at the cellular level. Autophagy is an essential process used by animal, plant, and fungal cells that allows for both recycling of macromolecular constituents under conditions of nutrient limitation and remodeling the intracellular struc...

Descripción completa

Detalles Bibliográficos
Autores principales: Baba, Misuzu, Osumi, Masako, Scott, Sidney V., Klionsky, Daniel J., Ohsumi, Yoshinori
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132654/
https://www.ncbi.nlm.nih.gov/pubmed/9412464
_version_ 1782142495023431680
author Baba, Misuzu
Osumi, Masako
Scott, Sidney V.
Klionsky, Daniel J.
Ohsumi, Yoshinori
author_facet Baba, Misuzu
Osumi, Masako
Scott, Sidney V.
Klionsky, Daniel J.
Ohsumi, Yoshinori
author_sort Baba, Misuzu
collection PubMed
description Stress conditions lead to a variety of physiological responses at the cellular level. Autophagy is an essential process used by animal, plant, and fungal cells that allows for both recycling of macromolecular constituents under conditions of nutrient limitation and remodeling the intracellular structure for cell differentiation. To elucidate the molecular basis of autophagic protein transport to the vacuole/lysosome, we have undertaken a morphological and biochemical analysis of this pathway in yeast. Using the vacuolar hydrolase aminopeptidase I (API) as a marker, we provide evidence that the autophagic pathway overlaps with the biosynthetic pathway, cytoplasm to vacuole targeting (Cvt), used for API import. Before targeting, the precursor form of API is localized mostly in restricted regions of the cytosol as a complex with spherical particles (termed Cvt complex). During vegetative growth, the Cvt complex is selectively wrapped by a membrane sac forming a double membrane-bound structure of ∼150 nm diam, which then fuses with the vacuolar membrane. This process is topologically the same as macroautophagy induced under starvation conditions in yeast (Baba, M., K. Takeshige, N. Baba, and Y. Ohsumi. 1994. J. Cell Biol. 124:903–913). However, in contrast with autophagy, API import proceeds constitutively in growing conditions. This is the first demonstration of the use of an autophagy-like mechanism for biosynthetic delivery of a vacuolar hydrolase. Another important finding is that when cells are subjected to starvation conditions, the Cvt complex is now taken up by an autophagosome that is much larger and contains other cytosolic components; depending on environmental conditions, the cell uses an alternate pathway to sequester the Cvt complex and selectively deliver API to the vacuole. Together these results indicate that two related but distinct autophagy-like processes are involved in both biogenesis of vacuolar resident proteins and sequestration of substrates to be degraded.
format Text
id pubmed-2132654
institution National Center for Biotechnology Information
language English
publishDate 1997
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21326542008-05-01 Two Distinct Pathways for Targeting Proteins from the Cytoplasm to the Vacuole/Lysosome Baba, Misuzu Osumi, Masako Scott, Sidney V. Klionsky, Daniel J. Ohsumi, Yoshinori J Cell Biol Article Stress conditions lead to a variety of physiological responses at the cellular level. Autophagy is an essential process used by animal, plant, and fungal cells that allows for both recycling of macromolecular constituents under conditions of nutrient limitation and remodeling the intracellular structure for cell differentiation. To elucidate the molecular basis of autophagic protein transport to the vacuole/lysosome, we have undertaken a morphological and biochemical analysis of this pathway in yeast. Using the vacuolar hydrolase aminopeptidase I (API) as a marker, we provide evidence that the autophagic pathway overlaps with the biosynthetic pathway, cytoplasm to vacuole targeting (Cvt), used for API import. Before targeting, the precursor form of API is localized mostly in restricted regions of the cytosol as a complex with spherical particles (termed Cvt complex). During vegetative growth, the Cvt complex is selectively wrapped by a membrane sac forming a double membrane-bound structure of ∼150 nm diam, which then fuses with the vacuolar membrane. This process is topologically the same as macroautophagy induced under starvation conditions in yeast (Baba, M., K. Takeshige, N. Baba, and Y. Ohsumi. 1994. J. Cell Biol. 124:903–913). However, in contrast with autophagy, API import proceeds constitutively in growing conditions. This is the first demonstration of the use of an autophagy-like mechanism for biosynthetic delivery of a vacuolar hydrolase. Another important finding is that when cells are subjected to starvation conditions, the Cvt complex is now taken up by an autophagosome that is much larger and contains other cytosolic components; depending on environmental conditions, the cell uses an alternate pathway to sequester the Cvt complex and selectively deliver API to the vacuole. Together these results indicate that two related but distinct autophagy-like processes are involved in both biogenesis of vacuolar resident proteins and sequestration of substrates to be degraded. The Rockefeller University Press 1997-12-29 /pmc/articles/PMC2132654/ /pubmed/9412464 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Baba, Misuzu
Osumi, Masako
Scott, Sidney V.
Klionsky, Daniel J.
Ohsumi, Yoshinori
Two Distinct Pathways for Targeting Proteins from the Cytoplasm to the Vacuole/Lysosome
title Two Distinct Pathways for Targeting Proteins from the Cytoplasm to the Vacuole/Lysosome
title_full Two Distinct Pathways for Targeting Proteins from the Cytoplasm to the Vacuole/Lysosome
title_fullStr Two Distinct Pathways for Targeting Proteins from the Cytoplasm to the Vacuole/Lysosome
title_full_unstemmed Two Distinct Pathways for Targeting Proteins from the Cytoplasm to the Vacuole/Lysosome
title_short Two Distinct Pathways for Targeting Proteins from the Cytoplasm to the Vacuole/Lysosome
title_sort two distinct pathways for targeting proteins from the cytoplasm to the vacuole/lysosome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132654/
https://www.ncbi.nlm.nih.gov/pubmed/9412464
work_keys_str_mv AT babamisuzu twodistinctpathwaysfortargetingproteinsfromthecytoplasmtothevacuolelysosome
AT osumimasako twodistinctpathwaysfortargetingproteinsfromthecytoplasmtothevacuolelysosome
AT scottsidneyv twodistinctpathwaysfortargetingproteinsfromthecytoplasmtothevacuolelysosome
AT klionskydanielj twodistinctpathwaysfortargetingproteinsfromthecytoplasmtothevacuolelysosome
AT ohsumiyoshinori twodistinctpathwaysfortargetingproteinsfromthecytoplasmtothevacuolelysosome