Characterising the role of the lysosomal membrane proteins MFSD1 and TMEM106b in osteoclasts

2016 ◽  
Author(s):  
David Massa Lopez ◽  
Markus Damme ◽  
Paul Saftig
Keyword(s):  
Membrane Proteins ◽  
Lysosomal Membrane ◽  
Lysosomal Membrane Proteins

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.

scholarly journals The role of lysosomal membrane proteins in glucose and lipid metabolism

2021 ◽  
Vol 35 (10) ◽  
Author(s):  
Jing Gu ◽  
Mengya Geng ◽  
Mengxiang Qi ◽  
Lizhuo Wang ◽  
Yao Zhang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Membrane Proteins ◽  
Lysosomal Membrane ◽  
Glucose And Lipid Metabolism ◽  
Lysosomal 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.

scholarly journals A dileucine signal situated in the C-terminal tail of the lysosomal membrane protein p40 is responsible for its targeting to lysosomes

2008 ◽  
Vol 414 (3) ◽  
pp. 431-440 ◽  
Author(s):  
Marielle Boonen ◽  
Roberta Rezende de Castro ◽  
Gaëlle Cuvelier ◽  
Isabelle Hamer ◽  
Michel Jadot
Keyword(s):  
Subcellular Fractionation ◽  
Lysosomal Membrane ◽  
Consensus Sequences ◽  
Cell Surface Biotinylation ◽  
Dileucine Motif ◽  
Lysosomal Sorting ◽  
Critical Residues ◽  
Lysosomal Membrane Proteins ◽  
Golgi Network

Transport of newly synthesized lysosomal membrane proteins from the TGN (trans-Golgi network) to the lysosomes is due to the presence of specific signals in their cytoplasmic domains that are recognized by cytosolic adaptors. p40, a hypothetical transporter of 372 amino acids localized in the lysosomal membrane, contains four putative lysosomal sorting motifs in its sequence: three of the YXXϕ-type (Y6QLF, Y106VAL, Y333NGL) and one of the [D/E]XXXL[L/I]-type (EQERL360L361). To test the role of these motifs in the biosynthetic transport of p40, we replaced the most critical residues of these consensus sequences, the tyrosine residue or the leucine–leucine pair, by alanine or alanine–valine respectively. We analysed the subcellular localization of the mutated p40 proteins in transfected HeLa cells by confocal microscopy and by biochemical approaches (subcellular fractionation on self-forming Percoll density gradients and cell surface biotinylation). The results of the present study show that p40 is mistargeted to the plasma membrane when its dileucine motif is disrupted. No role of the tyrosine motifs could be put forward. Taken together, our results provide evidence that the sorting of p40 from the TGN to the lysosomes is directed by the dileucine EQERL360L361 motif situated in its C-terminal tail.

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 Antibodies to platelets in patients with anti-phospholipid antibodies

Blood ◽  
1991 ◽  
Vol 77 (12) ◽  
pp. 2655-2659 ◽  
Author(s):  
HJ Out ◽  
PG de Groot ◽  
M van Vliet ◽  
GC de Gast ◽  
HK Nieuwenhuis ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Lysosomal Membrane ◽  
Immunofluorescence Method ◽  
Exact Role ◽  
Flow Cytofluorometry ◽  
Healthy Donors ◽  
Lysosomal Membrane Proteins ◽  
Lysosomal Membrane Protein ◽  
Platelet Autoantibodies

Abstract Binding of anti-phospholipid antibodies to circulating platelets and its consequences on platelet activation and aggregation was investigated in 11 patients with anti-phospholipid antibodies. Seven patients had mild thrombocytopenia. Nine healthy donors served as controls. Binding to platelets was investigated by performing enzyme- linked immunosorbent assays (ELISAs) with phospholipids as antigen on platelet eluates. Platelet activation was measured by flow cytofluorometry using monoclonal antibodies to an activation-specific lysosomal membrane protein. Findings in ELISA were compared with results of a conventional immunofluorescence method to detect platelet autoantibodies. In seven patients antibodies to negatively charged phospholipids were present in platelet eluates. In all thrombocytopenic patients and controls the platelets were not activated and aggregation was not impaired. There was a positive concordance of 50% between the results of immunofluorescence and ELISA. No apparent relation was found between the results of ELISA or immunofluorescence and platelet counts. It is concluded that anti-phospholipid antibodies can bind to circulating platelets. This binding is not associated with measurable aggregation abnormalities nor with platelet activation characterized by exposure of lysosomal membrane proteins. More studies are necessary to determine the exact role of anti-phospholipid antibodies in the pathogenesis of thrombocytopenia and thrombosis.

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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