Lysosomal TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism.

Autor: Takahashi H; Cellular Neuroscience, Neurodegeneration, Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT, 06536, USA., Perez-Canamas A; Cellular Neuroscience, Neurodegeneration, Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT, 06536, USA., Lee CW; Biomedical Research Institute of New Jersey (BRInj), Cedar Knolls, NJ, 07927, USA.; MidAtlantic Neonatology Associates (MANA), Morristown, NJ, 07960, USA.; Atlantic Health System, Morristown, NJ, 07960, USA., Ye H; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center At San Antonio, San Antonio, TX, 78229, USA., Han X; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center At San Antonio, San Antonio, TX, 78229, USA.; Department of Medicine, University of Texas Health Science Center At San Antonio, San Antonio, TX, 78229, USA., Strittmatter SM; Cellular Neuroscience, Neurodegeneration, Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT, 06536, USA. stephen.strittmatter@yale.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Sep 05; Vol. 7 (1), pp. 1088. Date of Electronic Publication: 2024 Sep 05.
DOI: 10.1038/s42003-024-06810-5
Abstrakt: TMEM106B is an endolysosomal transmembrane protein not only associated with multiple neurological disorders including frontotemporal dementia, Alzheimer's disease, and hypomyelinating leukodystrophy but also potentially involved in COVID-19. Additionally, recent studies have identified amyloid fibrils of C-terminal TMEM106B in both aged healthy and neurodegenerative brains. However, so far little is known about physiological functions of TMEM106B in the endolysosome and how TMEM106B is involved in a wide range of human conditions at molecular levels. Here, we performed lipidomic analysis of the brain of TMEM106B-deficient mice. We found that TMEM106B deficiency significantly decreases levels of two major classes of myelin lipids, galactosylceramide and its sulfated derivative sulfatide. Subsequent co-immunoprecipitation assay showed that TMEM106B physically interacts with galactosylceramidase. We also found that galactosylceramidase activity was significantly increased in TMEM106B-deficient brains. Thus, our results suggest that TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism and have implications for TMEM106B-associated diseases.
(© 2024. The Author(s).)
Databáze: MEDLINE
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