title: TECPR2 Cooperates with LC3C to Regulate COPII-Dependent ER Export.
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.
authors.affiliation: Institute of Biochemistry II, Medical School Goethe University, 60590 Frankfurt, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Stadel
authors.affiliation: Department of Biology, University of Konstanz, 78464 Konstanz, Germany; Biotechnology Institute Thurgau, 8280 Kreuzlingen, Switzerland.
authors.forename: Valentina
authors.initials: V
authors.lastname: Millarte
authors.affiliation: Department of Biology, University of Konstanz, 78464 Konstanz, Germany; Biotechnology Institute Thurgau, 8280 Kreuzlingen, Switzerland.
authors.forename: Kerstin D
authors.initials: KD
authors.lastname: Tillmann
authors.affiliation: Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, 60438 Frankfurt, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Huber
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Bat-Chen
authors.initials: BC
authors.lastname: Tamin-Yecheskel
authors.affiliation: Institute of Biochemistry II, Medical School Goethe University, 60590 Frankfurt, Germany; Buchmann Institute for Molecular Life Sciences, Goethe University, 60438 Frankfurt, Germany.
authors.forename: Masato
authors.initials: M
authors.lastname: Akutsu
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Alik
authors.initials: A
authors.lastname: Demishtein
authors.affiliation: Edmond and Lilly Safra Children's Hospital, Sheba Medical Center, Ramat Gan, 52621, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Bruria
authors.initials: B
authors.lastname: Ben-Zeev
authors.affiliation: Edmond and Lilly Safra Children's Hospital, Sheba Medical Center, Ramat Gan, 52621, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Anikster
authors.affiliation: Institute Curie, CNRS UMR144, Paris, 75248, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Perez
authors.affiliation: Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, 60438 Frankfurt, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Dötsch
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Zvulun
authors.initials: Z
authors.lastname: Elazar
authors.affiliation: Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, 60438 Frankfurt, Germany.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Rogov
authors.affiliation: Department of Biology, University of Konstanz, 78464 Konstanz, Germany; Biotechnology Institute Thurgau, 8280 Kreuzlingen, Switzerland.
authors.forename: Hesso
authors.initials: H
authors.lastname: Farhan
authors.affiliation: Institute of Biochemistry II, Medical School Goethe University, 60590 Frankfurt, Germany. Electronic address: behrends@em.uni-frankfurt.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Behrends
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C104378:BLOC1S1 protein, human; D002352:Carrier Proteins; C116741:GABARAP protein, human; C502071:MAP1LC3C protein, human; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C530641:SEC24D protein, human; C578280:TECPR2 protein, human; D033921:Vesicular Transport Proteins