TECPR2 Cooperates with LC3C to Regulate COPII-Dependent ER Export

Daniela Stadel, Valentina Millarte, Kerstin D. Tillmann, Jessica Huber, Bat Chen Tamin-Yecheskel, Masato Akutsu, Alik Demishtein, Bruria Ben-Zeev, Yair Anikster, Franck Perez, Volker Dötsch, Zvulun Elazar, Vladimir Rogov, Hesso Farhan, Christian Behrends*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

Hereditary spastic paraplegias (HSPs) are a diverse group of neurodegenerative diseases that are characterized by axonopathy of the corticospinal motor neurons. A mutation in the gene encoding for Tectonin β-propeller containing protein 2 (TECPR2) causes HSP that is complicated by neurological symptoms. While TECPR2 is a human ATG8 binding protein and positive regulator of autophagy, the exact function of TECPR2 is unknown. Here, we show that TECPR2 associates with several trafficking components, among them the COPII coat protein SEC24D. TECPR2 is required for stabilization of SEC24D protein levels, maintenance of functional ER exit sites (ERES), and efficient ER export in a manner dependent on binding to lipidated LC3C. TECPR2-deficient HSP patient cells display alterations in SEC24D abundance and ER export efficiency. Additionally, TECPR2 and LC3C are required for autophagosome formation, possibly through maintaining functional ERES. Collectively, these results reveal that TECPR2 functions as molecular scaffold linking early secretion pathway and autophagy.

Original languageEnglish
Pages (from-to)89-104
Number of pages16
JournalMolecular Cell
Volume60
Issue number1
DOIs
StatePublished - 2015

Funding

FundersFunder number
Swiss Science Foundation
Cluster of Excellence Frankfurt
Universität Konstanz
Deutschen Konsortium für Translationale Krebsforschung
State of Thurgau
Legacy Heritage Fund1309/13
European Research Council282333
German-Israeli Foundation GIF1129/157
Deutsche ForschungsgemeinschaftFA 961/3, BE 4685/1-1
Israel Science Foundation535/11

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