TY - JOUR
T1 - TECPR2 Cooperates with LC3C to Regulate COPII-Dependent ER Export
AU - Stadel, Daniela
AU - Millarte, Valentina
AU - Tillmann, Kerstin D.
AU - Huber, Jessica
AU - Tamin-Yecheskel, Bat Chen
AU - Akutsu, Masato
AU - Demishtein, Alik
AU - Ben-Zeev, Bruria
AU - Anikster, Yair
AU - Perez, Franck
AU - Dötsch, Volker
AU - Elazar, Zvulun
AU - Rogov, Vladimir
AU - Farhan, Hesso
AU - Behrends, Christian
N1 - Funding Information:
We are grateful to J.W. Harper for access to CompPASS. We thank L. Fisher, T. Proikas-Cezanne, N. Ktistakis, H. Stenmark, D. Popovic, D. McEwan, and members of the Behrends lab for critical reagents and helpful discussions. We are thankful to I. Dikic for generous support. This work was supported by grants from the German Cancer Consortium (DKTK), the Cluster of Excellence Frankfurt (Macromolecular Complexes), the Young Scholar Fund of the University of Konstanz, the Swiss Science Foundation, the State of Thurgau, the German Research Foundation (BE 4685/1-1; FA 961/3), and the European Research Council (282333). Z.E. is an incumbent of the Harold Korda Chair of Biology. We are grateful for funding from the Israel Science Foundation ISF (Grant #535/11), the German-Israeli Foundation GIF (Grant #1129/157), and the Legacy Heritage Fund (Grant #1309/13). Work in the Akutsu lab is funded by the Leibniz Award to I. Dikic.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molcel.2015.09.010
DO - 10.1016/j.molcel.2015.09.010
M3 - Article
C2 - 26431026
AN - SCOPUS:84951962450
SN - 1097-2765
VL - 60
SP - 89
EP - 104
JO - Molecular Cell
JF - Molecular Cell
IS - 1
ER -
