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000255139 1001_ $$aNalbach, Karsten$$b0
000255139 245__ $$aSpatial proteomics reveals secretory pathway disturbances caused by neuropathy-associated TECPR2.
000255139 260__ $$a[London]$$bNature Publishing Group UK$$c2023
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000255139 520__ $$aHereditary sensory and autonomic neuropathy 9 (HSAN9) is a rare fatal neurological disease caused by mis- and nonsense mutations in the gene encoding for Tectonin β-propeller repeat containing protein 2 (TECPR2). While TECPR2 is required for lysosomal consumption of autophagosomes and ER-to-Golgi transport, it remains elusive how exactly TECPR2 is involved in autophagy and secretion and what downstream sequels arise from defective TECPR2 due to its involvement in these processes. To address these questions, we determine molecular consequences of TECPR2 deficiency along the secretory pathway. By employing spatial proteomics, we describe pronounced changes with numerous proteins important for neuronal function being affected in their intracellular transport. Moreover, we provide evidence that TECPR2's interaction with the early secretory pathway is not restricted to COPII carriers. Collectively, our systematic profiling of a HSAN9 cell model points to specific trafficking and sorting defects which might precede autophagy dysfunction upon TECPR2 deficiency.
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000255139 650_2 $$2MeSH$$aCarrier Proteins: metabolism
000255139 650_2 $$2MeSH$$aSecretory Pathway
000255139 650_2 $$2MeSH$$aProteomics
000255139 650_2 $$2MeSH$$aProtein Transport
000255139 650_2 $$2MeSH$$aAutophagosomes
000255139 650_2 $$2MeSH$$aAutophagy: genetics
000255139 650_2 $$2MeSH$$aGolgi Apparatus
000255139 650_2 $$2MeSH$$aNerve Tissue Proteins: metabolism
000255139 650_7 $$2NLM Chemicals$$aCarrier Proteins
000255139 650_7 $$2NLM Chemicals$$aNerve Tissue Proteins
000255139 7001_ $$0P:(DE-2719)2812260$$aSchifferer, Martina$$b1
000255139 7001_ $$aBhattacharya, Debjani$$b2
000255139 7001_ $$00000-0003-2911-1559$$aHo-Xuan, Hung$$b3
000255139 7001_ $$aTseng, Wei$$b4
000255139 7001_ $$aWilliams, Luis A$$b5
000255139 7001_ $$00000-0002-3340-439X$$aStolz, Alexandra$$b6
000255139 7001_ $$0P:(DE-2719)2181459$$aLichtenthaler, Stefan F$$b7
000255139 7001_ $$00000-0002-3231-4464$$aElazar, Zvulun$$b8
000255139 7001_ $$00000-0002-9184-7607$$aBehrends, Christian$$b9
000255139 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-023-36553-6$$gVol. 14, no. 1, p. 870$$n1$$p870$$tNature Communications$$v14$$x2041-1723$$y2023
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