Fab1p PtdIns(3)P 5-Kinase Function Essential for Protein Sorting in the Multivesicular Body

Odorizzi, Greg; Babst, Markus; Emr, Scott D.

doi:10.1016/s0092-8674(00)81707-9

Cited by 619 publications

(734 citation statements)

References 50 publications

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“…These MVBs may thus act as a separate compartment and/or transport intermediates between the Golgi apparatus and the MVT ( Figure 5H). Collectively, these studies suggest that the MVBs and MVT are post-Golgi compartments and that they have the characteristic internal structure of late endosomes or lysosomes (Gruenberg and Maxfield, 1995;Odorizzi et al, 1998).…”

Section: Tubule Compartment Is a Multivesicular Post-golgi Compartmentmentioning

confidence: 84%

“…We now show that the MVT is a terminal lysosome compartment based on the following lines of evidence. First, the EM ultrastructural studies indicate that the MVT is a post-Golgi compartment with the same internal structure as late endosomes/lysosomes in other eukaryotic cells (Kobayashi et al, 1998;Odorizzi et al, 1998). Second, the MVT is labeled in a time-and temperature-dependent manner with the well-defined endocytic marker FM 4-64.…”

Section: Discussionmentioning

confidence: 99%

“…Significantly, they also show that the GFP moiety is delivered to the lumen of the MVT consistent with the finding that this protein is rapidly degraded when promastigotes are incubated in low pH medium. In yeast and animal cells, many membrane proteins are targeted to the vacuole/lysosome lumen via the recently described MVB pathway (Hirst et al, 1998;Kobayashi et al, 1998;Odorizzi et al, 1998;). In this pathway, membrane proteins destined for lysosomal degradation are transported from either the Golgi apparatus or the plasma membrane to the limiting membrane of late endosomes and subsequently incorporated into microinvaginating vesicles that are released into the luminal compartment.…”

Section: Discussionmentioning

confidence: 99%

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Regulated Degradation of an Endoplasmic Reticulum Membrane Protein in a Tubular Lysosome inLeishmania mexicana

Mullin¹,

Foth

Ilgoutz³

et al. 2001

MBoC

162

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The cell surface of the human parasite Leishmania mexicana is coated with glycosylphosphatidylinositol (GPI)-anchored macromolecules and free GPI glycolipids. We have investigated the intracellular trafficking of green fluorescent protein-and hemagglutinin-tagged forms of dolicholphosphate-mannose synthase (DPMS), a key enzyme in GPI biosynthesis in L. mexicana promastigotes. These functionally active chimeras are found in the same subcompartment of the endoplasmic reticulum (ER) as endogenous DPMS but are degraded as logarithmically growing promastigotes reach stationary phase, coincident with the down-regulation of endogenous DPMS activity and GPI biosynthesis in these cells. We provide evidence that these chimeras are constitutively transported to and degraded in a novel multivesicular tubule (MVT) lysosome. This organelle is a terminal lysosome, which is labeled with the endocytic marker FM 4-64, contains lysosomal cysteine and serine proteases and is disrupted by lysomorphotropic agents. Electron microscopy and subcellular fractionation studies suggest that the DPMS chimeras are transported from the ER to the lumen of the MVT via the Golgi apparatus and a population of 200-nm multivesicular bodies. In contrast, soluble ER proteins are not detectably transported to the MVT lysosome in either log or stationary phase promastigotes. Finally, the increased degradation of the DPMS chimeras in stationary phase promastigotes coincides with an increase in the lytic capacity of the MVT lysosome and changes in the morphology of this organelle. We conclude that lysosomal degradation of DPMS may be important in regulating the cellular levels of this enzyme and the stage-dependent biosynthesis of the major surface glycolipids of these parasites.

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Section: Tubule Compartment Is a Multivesicular Post-golgi Compartmentmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Regulated Degradation of an Endoplasmic Reticulum Membrane Protein in a Tubular Lysosome inLeishmania mexicana

Mullin¹,

Foth

Ilgoutz³

et al. 2001

MBoC

162

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“…Separate from its activity as an Rsp5 client, trafficking of Cps1 from the cell membrane to the vacuole has been well characterized and Cps1 is frequently used as a model cargo to study protein trafficking through MVBs (Odorizzi et al ., 1998). Using a quantitative, luciferase‐based assay to search for defects in MVB formation and sorting (Nickerson et al ., 2012; Nickerson & Merz, 2015), we observed that the original chr5 disome has a Cps1 trafficking defect that is ameliorated by the deletion of BUL1 or the bul1 Q146K allele (Fig.…”

Section: Resultsmentioning

confidence: 99%

Aneuploidy shortens replicative lifespan in Saccharomyces cerevisiae

et al. 2016

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SummaryAneuploidy and aging are correlated; however, a causal link between these two phenomena has remained elusive. Here, we show that yeast disomic for a single native yeast chromosome generally have a decreased replicative lifespan. In addition, the extent of this lifespan deficit correlates with the size of the extra chromosome. We identified a mutation in BUL1 that rescues both the lifespan deficit and a protein trafficking defect in yeast disomic for chromosome 5. Bul1 is an E4 ubiquitin ligase adaptor involved in a protein quality control pathway that targets membrane proteins for endocytosis and destruction in the lysosomal vacuole, thereby maintaining protein homeostasis. Concurrent suppression of the aging and trafficking phenotypes suggests that disrupted membrane protein homeostasis in aneuploid yeast may contribute to their accelerated aging. The data reported here demonstrate that aneuploidy can impair protein homeostasis, shorten lifespan, and may contribute to age‐associated phenotypes.

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“…In the classical endosome pathway, maturation involves Rab5 on early endosomes (EEs) and its exchange for Rab7 on late endosomes (LEs) and lysosomes (LYs) 5, 6. In addition, there is conversion of phosphatidylinositol 3‐phosphate (PtdIns(3)P) to PtdIns(3,5)P 2 , and progressive luminal acidification 7, 8, 9, 10, 11. As virus penetration and uncoating relies on the environment within maturing endosomes, it is perhaps no surprise that for many viruses, infection depends on factors involved in the maturation process 12, 13, 14.…”

mentioning

confidence: 99%

Vaccinia Virus Infection Requires Maturation of Macropinosomes

Rizopoulos

Balistreri

Kilcher

et al. 2015

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The prototypic poxvirus, vaccinia virus (VACV), occurs in two infectious forms, mature virions (MVs) and extracellular virions (EVs). Both enter HeLa cells by inducing macropinocytic uptake. Using confocal microscopy, live‐cell imaging, targeted RNAi screening and perturbants of endosome maturation, we analyzed the properties and maturation pathway of the macropinocytic vacuoles containing VACV MVs in HeLa cells. The vacuoles first acquired markers of early endosomes [Rab5, early endosome antigen 1 and phosphatidylinositol(3)P]. Prior to release of virus cores into the cytoplasm, they contained markers of late endosomes and lysosomes (Rab7a, lysosome‐associated membrane protein 1 and sorting nexin 3). RNAi screening of endocytic cell factors emphasized the importance of late compartments for VACV infection. Follow‐up perturbation analysis showed that infection required Rab7a and PIKfyve, confirming that VACV is a late‐penetrating virus dependent on macropinosome maturation. VACV EV infection was inhibited by depletion of many of the same factors, indicating that both infectious particle forms share the need for late vacuolar conditions for penetration.

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Fab1p PtdIns(3)P 5-Kinase Function Essential for Protein Sorting in the Multivesicular Body

Cited by 619 publications

References 50 publications

Regulated Degradation of an Endoplasmic Reticulum Membrane Protein in a Tubular Lysosome inLeishmania mexicana

Regulated Degradation of an Endoplasmic Reticulum Membrane Protein in a Tubular Lysosome inLeishmania mexicana

Aneuploidy shortens replicative lifespan in Saccharomyces cerevisiae

Vaccinia Virus Infection Requires Maturation of Macropinosomes

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