A previous study has reported that TMEM192 plays a role in supporting the growth of tumour cells. However, it does not exhibit any homologies to functionally characterized protein families. Īs listed in the NCBI HomoloGene database, TMEM192 has orthologues also in non-vertebrates like D. Furthermore, human TMEM192 forms homodimers, presumably mediated by the C-terminal domain of the protein. Only upon simultaneous ablation of both motifs, lysosomal delivery of TMEM192 was found to be impaired. Two dileucine motifs of the DXXLL type within the cytosolic N-terminal domain can independently initiate lysosomal targeting of the protein. In contrast to the majority of known lysosomal membrane proteins, human TMEM192 was found to be devoid of N-glycans. Subsequently, lysosomal localization of human TMEM192 upon overexpression and also under endogenous conditions was confirmed. One of these candidates was the Transmembrane protein 192, TMEM192, or FLJ38482, according to the previous nomenclature, which was initially reported in lysosomal membranes isolated from human placenta. These have identified several functionally uncharacterized integral membrane proteins with tentative lysosomal residence. Over the recent years important insights have been gained from systematic proteomic studies specifically analysing this subcompartment. This reflects that classical protein purification approaches have been difficult to apply to the analysis of hydrophobic membrane proteins. In contrast to the soluble lysosomal hydrolases the knowledge of the protein composition of the lysosomal membrane has remained fragmentary for much longer. Though more than 20 solute transport systems were demonstrated based on functional studies long ago, the identification and matching of the responsible proteins is still pending in many cases. In addition to providing a physical barrier, the lysosomal membrane harbours the vacuolar H + ATPase for acidification of the lumen and controls efflux of monomeric degradation products into the cytosol. Turnover of all types of biological macromolecules is achieved by more than 50 acidic hydrolases which are enclosed by a single phospholipid bilayer. Lysosomes are central catabolic organelles of eukaryotic cells degrading cell-intrinsic constituents delivered by autophagy as well as exogenous, endocytosed material. Further studies will be required to decipher its molecular function. Based on this, we conclude that under basal conditions in vivo the loss of TMEM192 can be efficiently compensated by alternative pathways. Furthermore, the abundance of the major immune cells was comparable in TMEM192 -/- and wild type mice. Histopathological, ultrastructural and biochemical analyses of all major tissues of TMEM192 -/- mice demonstrated normal lysosomal functions without apparent lysosomal storage. TMEM192 -/- murine embryonic fibroblasts (MEFs) exhibited a regular morphology of endo-/lysosomes and were capable of performing autophagy and lysosomal exocytosis. TMEM192 processing occurs after lysosomal targeting by pH-dependent lysosomal proteases. Thereby, a 17 kDa fragment is generated which was detected in most murine tissues except liver. Murine TMEM192 undergoes proteolytic processing in a tissue-specific manner. In brain, TMEM192 expression was pronounced in the hippocampus but also present in the cortex and cerebellum, as analysed based on a lacZ reporter allele. We reveal lysosomal residence of murine TMEM192 and demonstrate ubiquitous tissue expression. Therefore, we compared the biochemical properties of murine TMEM192 to those of the human orthologue. Here, we aimed to define the physiological role of TMEM192 by analysing consequences of TMEM192 ablation in mice. Upon TMEM192 knockdown in hepatoma cells, a dysregulation of autophagy and increased apoptosis were reported. Devoid of significant homologies, the molecular function of TMEM192 is currently unknown. TMEM192 exhibits four transmembrane segments with cytosolic N- and C-termini and forms homodimers. The Transmembrane protein 192 (TMEM192) is a lysosomal/late endosomal protein initially discovered by organellar proteomics. Received: JanuAccepted: ApPublished: ApAbstract Keywords: transmembrane protein 192, lysosome, lysosomal membrane, autophagy, proteolytic processing Thuy Linh Nguyen 1, Janna Schneppenheim 2, Sönke Rudnik 1, Renate Lüllmann-Rauch 2, Christian Bernreuther 3, Irm Hermans-Borgmeyer 4, Markus Glatzel 3, Paul Saftig 1 and Bernd Schröder 1ġ Biochemical Institute, Christian Albrechts University of Kiel, Kiel, GermanyĢ Institute of Anatomy, Christian Albrechts University of Kiel, Kiel, Germanyģ Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyĤ Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |