The molecular machinery for lysosome biogenesis*

Mullins, Chris; Bonifacino, Juan S.

doi:10.1002/bies.1048

Cited by 186 publications

(179 citation statements)

References 99 publications

Supporting

Mentioning

178

Contrasting

Order By: Relevance

“…Based on our results and those of others, we assume that the biogenesis of lysosomes is highly ascribed to the membrane traffic at early endosomes. Maturation and/or the 'kiss and run' model, rather than vesicle transport, may be feasible to explain why early endosomal dysfunction severely affects the morphology of lysosomes (Mullins and Bonifacino, 2001;Storrie and Desjardins, 1996).…”

Section: Discussionmentioning

confidence: 99%

Mammalian class E Vps proteins, SBP1 and mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase SKD1/Vps4B

Fujita

Yusuke

Imamura

et al. 2004

Journal of Cell Science

View full text Add to dashboard Cite

IntroductionIn eukaryotic cells, there are two major routes to the lysosome/vacuole after exiting the trans-Golgi network (TGN) (Hunziker and Geuze, 1996;Kornfeld and Mellman, 1989). One is the biosynthetic pathway by which the cell delivers newly synthesized lysosomal enzymes and membrane proteins for the biogenesis and maintenance of lysosomes/vacuoles. The transport vesicles carrying the cargo molecules are budded from the TGN and mostly target endosomes prior to arriving at lysosomes/vacuoles. The other route is the so-called endocytic pathway by which the cell delivers various internalized ligands and the receptors from the plasma membrane (PM) to lysosomes/vacuoles for degradation. The ligand-receptor complexes, for instance the EGF/EGF-receptor, are segregated into the internal vesicles of endosomes (Futter et al., 1996). Subsets of receptors that recycle back to the PM, such as transferrin receptor and low-density lipoprotein receptor, are sequestered into clathrin-coated vesicles at recycling endosomes and are removed from the degradative pathways. In both pathways, endosomes play central roles in the sorting of cargo molecules and indeed, endosomes are meeting places for membrane traffic from both routes.By an extensive genetic analysis in the yeast Saccharomyces cerevisiae, more than 50 of the Vps (vacuolar protein sorting) genes involved in membrane transport to vacuoles were isolated (Raymond et al., 1992). The class E Vps family, one of the sub-groups of Vps mutants, exhibits a modest degree of secretion of newly synthesized carboxypeptidase Y (CPY), a soluble vacuolar enzyme, compared with other sub-classes of Vps mutants. In class E Vps mutants, both the 60 kDa V-2997 SKD1 belongs to the AAA-ATPase family and is one of the mammalian class E Vps (vacuolar protein sorting) proteins. Previously we have reported that the overexpression of an ATPase activity-deficient form of SKD1 (suppressor of potassium transport growth defect), SKD1(E235Q), leads the perturbation of membrane transport through endosomes and lysosomes, however, the molecular mechanism behind the action of SKD1 is poorly understood. We have identified two SKD1-binding proteins, SBP1 and mVps2, by yeast two-hybrid screening and we assign them as mammalian class E Vps proteins. The primary sequence of SBP1 indicates 22.5% identity with that of Vta1p from Saccharomyces cerevisiae, which was recently identified as a novel class E Vps protein binding to Vps4p. In fact, SBP1 binds directly to SKD1 through its C-terminal region (198-309). Endogenous SBP1 is exclusively localized to cytosol, however it is redirected to an aberrant endosomal structure, the E235Q compartment, in the cells expressing SKD1(E235Q). The ATPase activity of SKD1 regulates both the membrane association of, and assembly of, a large hetero-oligomer protein complex, containing SBP1, which is potentially involved in membrane transport through endosomes and lysosomes. The N-terminal half (1-157) of human SBP1 is identical to lyst-interacting protein 5 and intriguingly, SKD...

show abstract

Section: Discussionmentioning

confidence: 99%

Mammalian class E Vps proteins, SBP1 and mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase SKD1/Vps4B

Fujita

Yusuke

Imamura

et al. 2004

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…The receptors are sorted within the endosomal system and relocalized to the internal vesicles of late endosomes or multivesicular bodies (MVBs), which then fuse with lysosomes. Intraluminal vesicles are then degraded by lipases, and associated proteins are degraded by proteases (Mullins and Bonifacino, 2001;Katzmann et al, 2002). The molecular mechanism for selection of receptors destined for down-regulation seems to be conserved through evolution from yeast to mammals.…”

Section: Introductionmentioning

confidence: 99%

The Growth-Regulatory Protein HCRP1/hVps37A Is a Subunit of Mammalian ESCRT-I and Mediates Receptor Down-Regulation

Bache

Slagsvold

Cabezas

et al. 2004

MBoC

145

129

View full text Add to dashboard Cite

The biogenesis of multivesicular bodies and endosomal sorting of membrane cargo are driven forward by the endosomal sorting complexes required for transport, ESCRT-I, -II, and -III. ESCRT-I is characterized in yeast as a complex consisting of Vps23, Vps28, and Vps37. Whereas mammalian homologues of Vps23 and Vps28 (named Tsg101 and hVps28, respectively) have been identified and characterized, a mammalian counterpart of Vps37 has not yet been identified. Here, we show that a regulator of proliferation, hepatocellular carcinoma related protein 1 (HCRP1), interacts with Tsg101, hVps28, and their upstream regulator Hrs. The ability of HCRP1 (which we assign the alternative name hVps37A) to interact with Tsg101 is conferred by its mod(r) domain and is shared with hVps37B and hVps37C, two other mod(r) domain-containing proteins. HCRP1 cofractionates with Tsg101 and hVps28 by size exclusion chromatography and colocalizes with hVps28 on LAMP1-positive endosomes. Whereas depletion of Tsg101 by siRNA reduces cellular levels of both hVps28 and HCRP1, depletion of HCRP1 has no effect on Tsg101 or hVps28. Nevertheless, HCRP1 depletion strongly retards epidermal growth factor (EGF) receptor degradation. Together, these results indicate that HCRP1 is a subunit of mammalian ESCRT-I and that its function is essential for lysosomal sorting of EGF receptors.

show abstract

“…Genetic analyses in yeast have led to the identification of over 70 proteins necessary for the transport and sorting of newly synthesized proteins to the yeast vacuole, an organelle that shares several characteristics with the lysosomes of higher animals 3 . These proteins control two major trafficking pathways from the trans-Golgi network (TGN) to the vacuole, the vacuolar protein sorting (VPS) and the adaptor protein (AP)-3-mediated sorting pathways [4][5][6] . Proteins trafficked via the VPS pathway transit through late endosomes/MVBs en route to the vacuole, whereas the AP-3 pathway mediates transport to the vacuole independently of the late endosomes/ MVBs.…”

mentioning

confidence: 99%

Bifurcation of the endocytic pathway into Rab5-dependent and -independent transport to the vacuole

et al. 2014

View full text Add to dashboard Cite

The yeast Rab5 homologue, Vps21p, is known to be involved both in the vacuolar protein sorting (VPS) pathway from the trans-Golgi network to the vacuole, and in the endocytic pathway from the plasma membrane to the vacuole. However, the intracellular location at which these two pathways converge remains unclear. In addition, the endocytic pathway is not completely blocked in yeast cells lacking all Rab5 genes, suggesting the existence of an unidentified route that bypasses the Rab5-dependent endocytic pathway. Here we show that convergence of the endocytic and VPS pathways occurs upstream of the requirement for Vps21p in these pathways. We also identify a previously unidentified endocytic pathway mediated by the AP-3 complex. Importantly, the AP-3-mediated pathway appears mostly intact in Rab5-disrupted cells, and thus works as an alternative route to the vacuole/ lysosome. We propose that the endocytic traffic branches into two routes to reach the vacuole: a Rab5-dependent VPS pathway and a Rab5-independent AP-3-mediated pathway.

show abstract

The molecular machinery for lysosome biogenesis*

Cited by 186 publications

References 99 publications

Mammalian class E Vps proteins, SBP1 and mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase SKD1/Vps4B

Mammalian class E Vps proteins, SBP1 and mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase SKD1/Vps4B

The Growth-Regulatory Protein HCRP1/hVps37A Is a Subunit of Mammalian ESCRT-I and Mediates Receptor Down-Regulation

Bifurcation of the endocytic pathway into Rab5-dependent and -independent transport to the vacuole

Contact Info

Product

Resources

About