Spatial proteomics reveals secretory pathway disturbances caused by neuropathy-associated TECPR2

Karsten Nalbach, Martina Schifferer, Debjani Bhattacharya, Hung Ho-Xuan, Wei Chou Tseng, Luis A. Williams, Alexandra Stolz, Stefan F. Lichtenthaler, Zvulun Elazar and Christian Behrends ()
Additional contact information
Karsten Nalbach: Ludwig-Maximilians-University München
Martina Schifferer: German Center for Neurodegenerative Diseases (DZNE)
Debjani Bhattacharya: Ludwig-Maximilians-University München
Hung Ho-Xuan: Goethe University Frankfurt
Wei Chou Tseng: Q-State Biosciences
Luis A. Williams: Q-State Biosciences
Alexandra Stolz: Goethe University Frankfurt
Stefan F. Lichtenthaler: German Center for Neurodegenerative Diseases (DZNE)
Zvulun Elazar: The Weizmann Institute of Science
Christian Behrends: Ludwig-Maximilians-University München

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract 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.

Date: 2023
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36553-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36553-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-36553-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().