Lysosomal targeting of autophagosomes by the TECPR domain of TECPR2
| Autor: | Oren Shatz, Zvulun Elazar, Milana Fraiberg, Nemanja Subic, Karsten Nalbach, Bat-Chen Tamim-Yecheskel, Bruria Ben-Zeev, Christian Behrends, Gali Heimer, Kamilya Kokabi, Franziska Eck |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
animal structures 030102 biochemistry & molecular biology Autophagy Neurodegeneration Autophagosomes Nerve Tissue Proteins Cell Biology Biology medicine.disease Domain (software engineering) Cell biology body regions 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Lysosome medicine Humans Lysosomal targeting Carrier Proteins Lysosomes Molecular Biology Research Paper |
| Zdroj: | Autophagy |
| ISSN: | 1554-8635 1554-8627 |
| Popis: | TECPR2 (tectonin beta-propeller repeat containing 2) is a large, multi-domain protein comprised of an amino-terminal WD domain, a middle unstructured region and a carboxy-terminal TEPCR domain comprises of six TECPR repeats followed by a functional LIR motif. Human TECPR2 mutations are linked to spastic paraplegia type 49 (SPG49), a hereditary neurodegenerative disorder. Here we show that basal macroautophagic/autophagic flux is impaired in SPG49 patient fibroblasts in the form of accumulated autophagosomes. Ectopic expression of either full length TECPR2 or the TECPR domain rescued autophagy in patient fibroblasts in a LIR-dependent manner. Moreover, this domain is recruited to the cytosolic leaflet of autophagosomal and lysosomal membranes in a LIR- and VAMP8-dependent manner, respectively. These findings provide evidence for a new role of the TECPR domain in particular, and TECPR2 in general, in lysosomal targeting of autophagosomes via association with Atg8-family proteins on autophagosomes and VAMP8 on lysosomes. Abbreviations: HOPS: homotypic fusion and vacuole protein sorting; LIR: LC3-interacting region; SPG49: spastic paraplegia type 49; STX17: syntaxin 17; TECPR2: tectonin beta-propeller repeat containing 2; VAMP8: vesicle associated membrane protein 8 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|