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000274095 1001_ $$aHeld, Sebastian$$b0
000274095 245__ $$aPhysiological shedding and C-terminal proteolytic processing of TMEM106B
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000274095 520__ $$aGenetic variants in TMEM106B, coding for a transmembrane protein of unknown function, have been identified as critical genetic modulators in various neurodegenerative diseases with a strong effect in patients with frontotemporal degeneration. The luminal domain of TMEM106B can form amyloid-like fibrils upon proteolysis. Whether this luminal domain is generated under physiological conditions and which protease(s) are involved in shedding remain unclear. We developed a commercially available antibody against the luminal domain of TMEM106B, allowing a detailed survey of the proteolytic processing under physiological conditions in cellular models and TMEM106B-related mouse models. Moreover, fibrillary TMEM106B was detected in human autopsy material. We find that the luminal domain is generated by multiple lysosomal cysteine-type proteases. Cysteine-type proteases perform additional C-terminal trimming, for which experimental evidence has been lacking. The presented results allow an in-depth perception of the processing of TMEM106B, a prerequisite to understanding factors leading to fibril formation.
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000274095 7001_ $$aErck, Christian$$b1
000274095 7001_ $$00000-0001-5372-1918$$aKemppainen, Susanna$$b2
000274095 7001_ $$00000-0001-8685-4514$$aBleibaum, Florian$$b3
000274095 7001_ $$00000-0001-6544-4102$$aGiridhar, Neha Jadhav$$b4
000274095 7001_ $$0P:(DE-2719)2812867$$aFeederle, Regina$$b5
000274095 7001_ $$0P:(DE-2719)9002298$$aKrenner, Claudia$$b6$$udzne
000274095 7001_ $$00009-0009-0810-1213$$aJuopperi, Sini-Pauliina$$b7
000274095 7001_ $$00009-0006-6834-0425$$aCalliari, Anna$$b8
000274095 7001_ $$00000-0003-4570-8734$$aMentrup, Torben$$b9
000274095 7001_ $$00000-0003-0774-6270$$aSchröder, Bernd$$b10
000274095 7001_ $$00000-0001-7189-7917$$aDickson, Dennis W.$$b11
000274095 7001_ $$00000-0002-2250-327X$$aRauramaa, Tuomas$$b12
000274095 7001_ $$00000-0003-2959-129X$$aPetrucelli, Leonard$$b13
000274095 7001_ $$00000-0002-4894-4858$$aPrudencio, Mercedes$$b14
000274095 7001_ $$00000-0002-1355-6716$$aHiltunen, Mikko$$b15
000274095 7001_ $$00000-0002-3883-6554$$aLüningschrör, Patrick$$b16
000274095 7001_ $$0P:(DE-2719)9000368$$aCapell, Anja$$b17
000274095 7001_ $$00000-0002-9699-9351$$aDamme, Markus$$b18
000274095 773__ $$0PERI:(DE-600)2649101-1$$a10.1016/j.celrep.2024.115107$$gVol. 44, no. 1, p. 115107 -$$n1$$p115107$$tCell reports$$v44$$x2211-1247$$y2025
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