scholarly journals A conserved ubiquitin- and ESCRT-dependent pathway to regulate human lysosomal membrane proteins

2020 ◽  
Author(s):  
Weichao Zhang ◽  
Xi Yang ◽  
Liang Chen ◽  
Yun-Yu Liu ◽  
Varsha Venkatarangan ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Cellular Materials ◽  
Lysosomal Membrane ◽  
Dependent Manner ◽  
Endosomal Sorting ◽  
Escrt Machinery ◽  
Lysosomal Membrane Proteins ◽  
Nutrient Homeostasis ◽  
Lysosome Membrane ◽  
Dependent Pathway

AbstractThe lysosome is an essential organelle to recycle cellular materials and maintain nutrient homeostasis, but the mechanism to down-regulate lysosomal membrane proteins is poorly understood. In this study, we developed a cycloheximide chase assay to measure the half-lives of ~30 human lysosomal membrane proteins, and identified RNF152 as a short-lived protein. The degradation of RNF152 depends on ubiquitin and the endosomal sorting complexes required for transport (ESCRT) machinery. Ubiquitinated RNF152 is sorted and internalized by the ESCRT machinery into the lysosomal lumen for degradation. Strikingly, when expressed in budding yeast, human RNF152 is also degraded by the vacuole (yeast lysosome) in an ESCRT-dependent manner. Thus, our study uncovered a conserved mechanism to down-regulate lysosome membrane proteins.

scholarly journals A  conserved ubiquitin- and ESCRT-dependent pathway internalizes human lysosomal membrane proteins for degradation

PLoS Biology ◽  
2021 ◽  
Vol 19 (7) ◽  
pp. e3001361
Author(s):  
Weichao Zhang ◽  
Xi Yang ◽  
Liang Chen ◽  
Yun-Yu Liu ◽  
Varsha Venkatarangan ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Lysosomal Membrane ◽  
Dependent Manner ◽  
Endosomal Sorting ◽  
Escrt Machinery ◽  
Lysosomal Membrane Proteins ◽  
Carboxyl Terminal ◽  
Nutrient Homeostasis ◽  
Lysosome Membrane ◽  
Dependent Pathway

The lysosome is an essential organelle to recycle cellular materials and maintain nutrient homeostasis, but the mechanism to down-regulate its membrane proteins is poorly understood. In this study, we performed a cycloheximide (CHX) chase assay to measure the half-lives of approximately 30 human lysosomal membrane proteins (LMPs) and identified RNF152 and LAPTM4A as short-lived membrane proteins. The degradation of both proteins is ubiquitin dependent. RNF152 is a transmembrane E3 ligase that ubiquitinates itself, whereas LAPTM4A uses its carboxyl-terminal PY motifs to recruit NEDD4-1 for ubiquitination. After ubiquitination, they are internalized into the lysosome lumen by the endosomal sorting complexes required for transport (ESCRT) machinery for degradation. Strikingly, when ectopically expressed in budding yeast, human RNF152 is still degraded by the vacuole (yeast lysosome) in an ESCRT-dependent manner. Thus, our study uncovered a conserved mechanism to down-regulate lysosome membrane proteins.

Lysosomal membrane proteins exposed to melanin in melanocyte B16F10

2016 ◽  
Vol 8 (3) ◽  
pp. 253-257
Author(s):  
Seung Hyuck Bang ◽  
Dong Jun Park ◽  
Yang-Hoon Kim ◽  
Jiho Min
Keyword(s):  
Membrane Proteins ◽  
Lysosomal Membrane ◽  
Lysosomal Membrane Proteins

scholarly journals NCU-G1 is a highly glycosylated integral membrane protein of the lysosome

2009 ◽  
Vol 422 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Oliver Schieweck ◽  
Markus Damme ◽  
Bernd Schröder ◽  
Andrej Hasilik ◽  
Bernhard Schmidt ◽  
...  
Keyword(s):  
Amino Acid ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Mouse Liver ◽  
Lysosomal Membrane ◽  
Molecular Forms ◽  
Type I ◽  
Calculated Molecular Mass ◽  
Sorting Motif ◽  
Lysosomal Membrane Proteins

Until recently, a modest number of approx. 40 lysosomal membrane proteins had been identified and even fewer were characterized in their function. In a proteomic study, using lysosomal membranes from human placenta we identified several candidate lysosomal membrane proteins and proved the lysosomal localization of two of them. In the present study, we demonstrate the lysosomal localization of the mouse orthologue of the human C1orf85 protein, which has been termed kidney-predominant protein NCU-G1 (GenBank® accession number: AB027141). NCU-G1 encodes a 404 amino acid protein with a calculated molecular mass of 39 kDa. The bioinformatics analysis of its amino acid sequence suggests it is a type I transmembrane protein containing a single tyrosine-based consensus lysosomal sorting motif at position 400 within the 12-residue C-terminal tail. Its lysosomal localization was confirmed using immunofluorescence with a C-terminally His-tagged NCU-G1 and the lysosomal marker LAMP-1 (lysosome-associated membrane protein-1) as a reference, and by subcellular fractionation of mouse liver after a tyloxapol-induced density shift of the lysosomal fraction using an anti-NCU-G1 antiserum. In transiently transfected HT1080 and HeLa cells, the His-tagged NCU-G1 was detected in two molecular forms with apparent protein sizes of 70 and 80 kDa, and in mouse liver the endogenous wild-type NCU-G1 was detected as a 75 kDa protein. The remarkable difference between the apparent and the calculated molecular masses of NCU-G1 was shown, by digesting the protein with N-glycosidase F, to be due to an extensive glycosylation. The lysosomal localization was impaired by mutational replacement of an alanine residue for the tyrosine residue within the putative sorting motif.

The Response of Liposomes Modified with Lysosomal Membrane Proteins to the Targeting Ability Associated with Antimicrobial Activity

2018 ◽  
Vol 14 (12) ◽  
pp. 2198-2207
Author(s):  
Seung Hyuck Bang ◽  
Ra-Mi Park ◽  
Simranjeet Singh Sekhon ◽  
Geun Woo Lee ◽  
Yang-Hoon Kim ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Membrane Proteins ◽  
Lysosomal Membrane ◽  
Lysosomal Membrane Proteins ◽  
Targeting Ability

scholarly journals Glycolipid-Dependent Sorting of Melanosomal from Lysosomal Membrane Proteins by Lumenal Determinants

Traffic ◽  
2008 ◽  
Vol 9 (6) ◽  
pp. 951-963 ◽  
Author(s):  
Sophie Groux-Degroote ◽  
Suzanne M. van Dijk ◽  
Jasja Wolthoorn ◽  
Sylvia Neumann ◽  
Alexander C. Theos ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Lysosomal Membrane ◽  
Lysosomal Membrane Proteins
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