@article{f6fa30c9bd0445ce829ace07b4a1eceb,
title = "TFG binds LC3C to regulate ULK1 localization and autophagosome formation",
abstract = "The early secretory pathway and autophagy are two essential and evolutionarily conserved endomembrane processes that are finely interlinked. Although growing evidence suggests that intracellular trafficking is important for autophagosome biogenesis, the molecular regulatory network involved is still not fully defined. In this study, we demonstrate a crucial effect of the COPII vesicle-related protein TFG (Trk-fused gene) on ULK1 puncta number and localization during autophagy induction. This, in turn, affects formation of the isolation membrane, as well as the correct dynamics of association between LC3B and early ATG proteins, leading to the proper formation of both omegasomes and autophagosomes. Consistently, fibroblasts derived from a hereditary spastic paraparesis (HSP) patient carrying mutated TFG (R106C) show defects in both autophagy and ULK1 puncta accumulation. In addition, we demonstrate that TFG activity in autophagy depends on its interaction with the ATG8 protein LC3C through a canonical LIR motif, thereby favouring LC3C-ULK1 binding. Altogether, our results uncover a link between TFG and autophagy and identify TFG as a molecular scaffold linking the early secretion pathway to autophagy.",
keywords = "autophagy, ERGIC, LC3C, TFG",
author = "Marianna Carinci and Beatrice Testa and Matteo Bordi and Giacomo Milletti and Massimo Bonora and Laura Antonucci and Caterina Ferraina and Marta Carro and Mukesh Kumar and Donatella Ceglie and Franziska Eck and Roberta Nardacci and {le Guerrou{\'e}}, Francois and Stefania Petrini and Soriano, {Maria E.} and Ignazio Caruana and Valentina Doria and Maria Manifava and Camille Peron and Matteo Lambrughi and Valeria Tiranti and Christian Behrends and Elena Papaleo and Paolo Pinton and Carlotta Giorgi and Ktistakis, {Nicholas T.} and Franco Locatelli and Francesca Nazio and Francesco Cecconi",
note = "Funding Information: We are grateful to S. Walker for the technical assistance. We thank the {"}Cell lines and DNA Bank of Genetic Movement Disorders and Mitochondrial Diseases” of the Telethon Network of Genetic Biobanks (grant GTB12001J). Francesco Cecconi{\textquoteright}s laboratory is supported by grants from the Danish Cancer Society (KBVU R72‐A4408, R146‐A9364, R231‐A14034), the Novo Nordisk Foundation (NNF13OC0007559, NNF16OC0022544), the Lundbeckfonden (R233‐2016‐3360), the LEO Foundation (LF17024), “Associazione Italiana per la Ricerca sul Cancro” (AIRC project IG 2019 #23543) and The Italian Ministry of Research (MIUR, project PRIN 2017 FS5SHL Radius). F. Cecconi{\textquoteright}s and E. Papaleo{\textquoteright}s laboratories in Copenhagen are part of the Center of Excellence for Autophagy, Recycling and Disease (CARD), funded by the Danmarks Grundforskningsfond (DNRF125), Carlsberg fondet Distinguished Fellowship (CF18‐0314) to E.P. and a Netaji Subhash ICAR international fellowship (Govt. of India) to M.K. This research was also supported in part by grants from the Italian Ministry of Health (Ricerca corrente) to F. Nazio; the Italian Ministry of Education, University and Research (Research Project of National Relevance 2017 ID 2017WC8499) to F. Locatelli; and AIRC (Associazione Italiana Ricerca sul Cancro, 5x1000 ID 9962 and AIRC IG 2018 ID 21724) to F. Locatelli. This work is in part supported by European Research Council Grant 853057‐InflaPML (to C.G.) and EMBO Short‐Term Fellowship (number 7463) to M. Carinci. We give a special thanks to Vanda Turcanova for her help with cloning and mutagenesis, and Dr. Cristina Valacca, (Copenhagen) Prof. Silvia Campello, Dr. Valentina Cianfanelli and Dr. Carlo Rodolfo (Rome) for their strenuous help and support. C.B. was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) within the frameworks of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198) and of the Collaborative Research Center 1177 (ID 259130777). Publisher Copyright: {\textcopyright}2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license",
year = "2021",
month = may,
day = "17",
doi = "10.15252/embj.2019103563",
language = "English",
volume = "40",
pages = "1--18",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "10",
}