Integral and Associated Lysosomal Membrane Proteins

Abstract

We searched for novel proteins in lysosomal membranes, tentatively participating in molecular transport across the membrane and/or in interactions with other compartments. In membranes purified from placental lysosomes, we identified 58 proteins, known to reside at least partially in the lysosomal membrane. These included 17 polypeptides comprising or associated with the vacuolar adenosine triphosphatase. We report on additional 86 proteins that were significantly enriched in the lysosomal membrane fraction. Among these, 12 novel proteins of unknown functions were found. Three were orthologues of rat proteins that have been identified in tritosomes by Bagshaw RD et al. (A proteomic analysis of lysosomal integral membrane proteins reveals the diverse composition of the organelle. Mol Cell Proteomics 2005;4:133-143). Here, the proteins encoded by LOC201931 (FLJ38482) and LOC51622 (C7orf28A) were expressed with an appended fluorescent tag in HeLa cells and found to be present in lysosomal organelles. Among the lysosomally enriched proteins, also 16 enzymes and transporters were detected that had not been assigned to lysosomal membranes previously. Finally, our results identified a particular set of proteins with known functions in signaling and targeting to be at least partially associated with lysosomes.

Protein composition of the hepatitis A virus quasi-envelope

“…However, DPP4, CD9, and EPCAM have each been identified in exosomes from a variety of cell types (17-19) (Vesiclepedia database), likely reflecting ambiguity in their membrane associations. Indeed, despite its use as a marker of apical membrane polarity, DPP4 is a well-established lysosomal membrane component (20).…”

“…3). This includes DPP4, which, although an integral apical transmembrane protein, is also associated with lysosomes (20). No array of proteins has been shown to be completely specific for exosomes versus other types of extracellular vesicles formed by outward budding at the plasma membrane rather than inward budding into MVBs (17).…”

SLC46A3 Is Required to Transport Catabolites of Noncleavable Antibody Maytansine Conjugates from the Lysosome to the Cytoplasm

“…Screens employing two distinct custom shRNA libraries were performed to identify genes involved in noncleavable linker maytansine ADC (anti-CD70 Ab-MCC-DM1) catabolite transport from the lysosome to cytoplasm. Library 1 contained genes annotated as membrane proteins, predominantly cell surface proteins, while cancerres.aacrjournals.org Downloaded from library 2 was designed to include genes annotated to have transporter function or lysosomal localization (20)(21)(22), approximately 35 amino acid transporter genes, and genes that regulate lysosomal function consisting of 14 lysosmal ATPase subunits. The shRNA libraries were screened in 786-0 cells using cell survival as a readout (Fig.…”

Mannose 6 Dephosphorylation of Lysosomal Proteins Mediated by Acid Phosphatases Acp2 and Acp5

“…These catabolic functions of lysosomes are catalyzed by more than 50 different soluble acid hydrolases and accessory activator proteins (29). The hydrolases are separated from the cytoplasm by a lysosomal membrane composed of about 140 highly glycosylated membrane proteins (2,42,43). In addition, the lipid composition of lysosomal membranes differs from that of plasma membranes or other limiting membranes of subcellular compartments and is characterized by a low cholesterol and an enriched anionic lipid content (44).…”