ATG9A is the only polytopic protein of the mammalian autophagy-related protein family whose members regulate autophagosome formation during macroautophagy. At steady state, ATG9A localizes to several intracellular sites, including the Golgi apparatus, endosomes and the plasma membrane, and it redistributes towards autophagosomes upon autophagy induction. Interestingly, the transport of yeast Atg9 to the pre-autophagosomal structure depends on its self-association, which is mediated by a short amino acid motif located in the C-terminal region of the protein. Here, we investigated whether the residues that align with this motif in human ATG9A (V515-C519) are also required for its trafficking in mammalian cells. Interestingly, our findings support that human ATG9A self-interacts as well, and that this process promotes transport of ATG9A molecules through the Golgi apparatus. Furthermore, our data reveal that the transport of ATG9A out of the ER is severely impacted after mutation of the conserved V515-C519 motif. Nevertheless, the mutated ATG9A molecules could still interact with each other, indicating that the molecular mechanism of self-interaction differs in mammalian cells compared to yeast. Using sequential amino acid substitutions of glycine 516 and cysteine 519, we found that the stability of ATG9A relies on both of these residues, but that only the former is required for efficient transport of human ATG9A from the endoplasmic reticulum to the Golgi apparatus.
|Pages (de - à)||404-409|
|Nombre de pages||6|
|journal||Biochemical and Biophysical Research Communications|
|Numéro de publication||2|
|Etat de la publication||Publié - 14 oct. 2016|
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Plateforme technologique Caracterisation physico-chimiques
Equipement/installations: Plateforme technolgique
Thèses de l'étudiant
Identification des déterminants moléculaires impliqués dans le transport d'ATG9A (autophagy-related protein 9A) à partir du réticulum endoplasmique en conditions basalesAuteur: Staudt, C., 24 juil. 2017
Superviseur: Jadot, M. (Promoteur), Boonen, M. (Copromoteur), Poumay, Y. (Président), ANDRE, B. (Personne externe) (Jury), Chainiaux, F. (Jury), De Bolle, X. (Jury), Flamion, B. (Jury) & Morsomme, P. (Personne externe) (Jury)
Student thesis: Doc types › Docteur en Sciences