TY  - JOUR
AU  - Nalbach, Karsten
AU  - Schifferer, Martina
AU  - Bhattacharya, Debjani
AU  - Ho-Xuan, Hung
AU  - Tseng, Wei
AU  - Williams, Luis A
AU  - Stolz, Alexandra
AU  - Lichtenthaler, Stefan F
AU  - Elazar, Zvulun
AU  - Behrends, Christian
TI  - Spatial proteomics reveals secretory pathway disturbances caused by neuropathy-associated TECPR2.
JO  - Nature Communications
VL  - 14
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2023-00258
SP  - 870
PY  - 2023
N1  - CC BY
AB  - Hereditary 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.
KW  - Carrier Proteins: metabolism
KW  - Secretory Pathway
KW  - Proteomics
KW  - Protein Transport
KW  - Autophagosomes
KW  - Autophagy: genetics
KW  - Golgi Apparatus
KW  - Nerve Tissue Proteins: metabolism
KW  - Carrier Proteins (NLM Chemicals)
KW  - Nerve Tissue Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36797266
C2  - pmc:PMC9935918
DO  - DOI:10.1038/s41467-023-36553-6
UR  - https://pub.dzne.de/record/255139
ER  -