scholarly journals Endolyn is a mucin-like type I membrane protein targeted to lysosomes by its cytoplasmic tail

2000 ◽  
Vol 345 (2) ◽  
pp. 287-296 ◽  
Author(s):  
Gudrun IHRKE ◽  
Sally R. GRAY ◽  
J. Paul LUZIO
Keyword(s):  
Amino Acids ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Mammalian Cells ◽  
Core Protein ◽  
Rat Kidney ◽  
Cytoplasmic Tail ◽  
Lysosomal Membrane ◽  
Type I ◽  
Lysosomal Membrane Proteins

Endolyn (endolyn-78) is a membrane protein found in lysosomal and endosomal compartments of mammalian cells. Unlike ‘classical’ lysosomal membrane proteins, such as lysosome-associated membrane protein (lamp)-1, it is also present in a subapical compartment in polarized WIF-B hepatocytes. The structural features that determine sorting of endolyn are unknown. We have identified a rat endolyn cDNA by expression screening. The cDNA encodes a ubiquitously expressed type I membrane protein with a short cytoplasmic tail of 13 amino acids and many putative sites for N- and O-linked glycosylation in the predicted luminal domain. Endolyn is closely related to two human mucin-like proteins, multi-glycosylated core protein (MGC)-24 and CD164 (MGC-24v), expressed in gastric carcinoma cells and bone marrow stromal and haematopoietic precursor cells respectively. The predicted transmembrane and cytoplasmic tail domains of endolyn, as well as parts of its luminal domain, also show some similarities with lamp-1 and lamp-2. Like these and other known lysosomal membrane proteins, endolyn contains a YXXØ motif at the C-terminus of its cytoplasmic tail (where Ø is a bulky hydrophobic amino acid), but with no preceding glycine. Nonetheless, the last ten amino acids of this tail, when transplanted on to human CD8, caused efficient targeting of the chimaeric protein to endosomes and lysosomes in transfected normal rat kidney cells.

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.

Lysosomal membrane proteins: life between acid and neutral conditions

2010 ◽  
Vol 38 (6) ◽  
pp. 1420-1423 ◽  
Author(s):  
Paul Saftig ◽  
Bernd Schröder ◽  
Judith Blanz
Keyword(s):  
Membrane Proteins ◽  
Membrane Protein ◽  
Hydrolytic Degradation ◽  
Cell Types ◽  
Transport Processes ◽  
Lysosomal Membrane ◽  
Cell Physiology ◽  
Depth Analysis ◽  
Lysosomal Membrane Proteins

Whereas we have a profound understanding about the function and biogenesis of the protein constituents in the lumen of the lysosomal compartment, much less is known about the functions of proteins of the lysosomal membrane. Proteomic analyses of the lysosomal membrane suggest that, apart from the well-known lysosomal membrane proteins, additional and less abundant membrane proteins are present. The identification of disease-causing genes and the in-depth analysis of knockout mice leading to mutated or absent membrane proteins of the lysosomal membrane have demonstrated the essential role of these proteins in lysosomal acidification, transport of metabolites resulting from hydrolytic degradation and interaction and fusion with other cellular membrane systems. In addition, trafficking pathways of lysosomal membrane proteins are closely linked to the biogenesis of this compartment. This is exemplified by the recent finding that LIMP-2 (lysosomal integral membrane protein type-2) is responsible for the mannose 6-phosphate receptor-independent delivery of newly synthesized β-glucocerebrosidase to the lysosome. Similar to LIMP-2, which could also be linked to vesicular transport processes in certain polarized cell types, the major constituents of the lysosomal membrane, the glycoproteins LAMP (lysosome-associated membrane protein)-1 and LAMP-2 are essential for regulation of lysosomal motility and participating in control of membrane fusion events between autophagosomes or phagosomes with late endosomes/lysosomes. Our recent investigations into the role of these proteins have not only increased our understanding of the endolysosomal system, but also supported their major role in cell physiology and the development of different diseases.

TMCC3 localizes at the three-way junctions for the proper tubular network of the endoplasmic reticulum

2019 ◽  
Vol 476 (21) ◽  
pp. 3241-3260
Author(s):  
Sindhu Wisesa ◽  
Yasunori Yamamoto ◽  
Toshiaki Sakisaka
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Mammalian Cells ◽  
Coiled Coil ◽  
Transmembrane Domains ◽  
Domain Family ◽  
Coiled Coil Domain ◽  
U2os Cells ◽  
Er Membrane

The tubular network of the endoplasmic reticulum (ER) is formed by connecting ER tubules through three-way junctions. Two classes of the conserved ER membrane proteins, atlastins and lunapark, have been shown to reside at the three-way junctions so far and be involved in the generation and stabilization of the three-way junctions. In this study, we report TMCC3 (transmembrane and coiled-coil domain family 3), a member of the TEX28 family, as another ER membrane protein that resides at the three-way junctions in mammalian cells. When the TEX28 family members were transfected into U2OS cells, TMCC3 specifically localized at the three-way junctions in the peripheral ER. TMCC3 bound to atlastins through the C-terminal transmembrane domains. A TMCC3 mutant lacking the N-terminal coiled-coil domain abolished localization to the three-way junctions, suggesting that TMCC3 localized independently of binding to atlastins. TMCC3 knockdown caused a decrease in the number of three-way junctions and expansion of ER sheets, leading to a reduction of the tubular ER network in U2OS cells. The TMCC3 knockdown phenotype was partially rescued by the overexpression of atlastin-2, suggesting that TMCC3 knockdown would decrease the activity of atlastins. These results indicate that TMCC3 localizes at the three-way junctions for the proper tubular ER network.

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

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 Transient translocation of the cytoplasmic (endo) domain of a type I membrane glycoprotein into cellular membranes.

1993 ◽  
Vol 120 (4) ◽  
pp. 877-883 ◽  
Author(s):  
N Liu ◽  
D T Brown
Keyword(s):  
Amino Acids ◽  
Membrane Protein ◽  
Signal Sequence ◽  
Attachment Site ◽  
Integral Membrane Protein ◽  
Carboxyl Terminus ◽  
Type I ◽  
E2 Glycoprotein ◽  
Typical Type ◽  
Membrane Spanning

The E2 glycoprotein of the alphavirus Sindbis is a typical type I membrane protein with a single membrane spanning domain and a cytoplasmic tail (endo domain) containing 33 amino acids. The carboxyl terminal domain of the tail has been implicated as (a) attachment site for nucleocapsid protein, and (b) signal sequence for integration of the other alpha-virus membrane proteins 6K and E1. These two functions require that the carboxyl terminus be exposed in the cell cytoplasm (a) and exposed in the lumen of the endoplasmic reticulum (b). We have investigated the orientation of this glycoprotein domain with respect to cell membranes by substituting a tyrosine for the normally occurring serine, four amino acids upstream of the carboxyl terminus. Using radioiodination of this tyrosine as an indication of the exposure of the glycoprotein tail, we have provided evidence that this domain is initially translocated into a membrane and is returned to the cytoplasm after export from the ER. This is the first demonstration of such a transient translocation of a single domain of an integral membrane protein and this rearrangement explains some important aspects of alphavirus assembly.

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

scholarly journals Protein Networks Supporting AP-3 Function in Targeting Lysosomal Membrane Proteins

2008 ◽  
Vol 19 (5) ◽  
pp. 1942-1951 ◽  
Author(s):  
Thorsten Baust ◽  
Mihaela Anitei ◽  
Cornelia Czupalla ◽  
Iryna Parshyna ◽  
Line Bourel ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Brefeldin A ◽  
Lysosomal Membrane ◽  
Exchange Factor ◽  
Proteomic Screen ◽  
Early Endosomes ◽  
Lysosomal Membrane Proteins ◽  
Guanosine Triphosphatase ◽  
Phosphatidylinositol 3

The AP-3 adaptor complex targets selected transmembrane proteins to lysosomes and lysosome-related organelles. We reconstituted its preferred interaction with liposomes containing the ADP ribosylation factor (ARF)-1 guanosine triphosphatase (GTPase), specific cargo tails, and phosphatidylinositol-3 phosphate, and then we performed a proteomic screen to identify new proteins supporting its sorting function. We identified ≈30 proteins belonging to three networks regulating either AP-3 coat assembly or septin polymerization or Rab7-dependent lysosomal transport. RNA interference shows that, among these proteins, the ARF-1 exchange factor brefeldin A-inhibited exchange factor 1, the ARF-1 GTPase-activating protein 1, the Cdc42-interacting Cdc42 effector protein 4, an effector of septin-polymerizing GTPases, and the phosphatidylinositol-3 kinase IIIC3 are key components regulating the targeting of lysosomal membrane proteins to lysosomes in vivo. This analysis reveals that these proteins, together with AP-3, play an essential role in protein sorting at early endosomes, thereby regulating the integrity of these organelles.

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