Huntingtin facilitates selective autophagy
| Autor: | Zvulun Elazar, Amir Gelman, Moran Rawet-Slobodkin |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Scaffold protein
congenital hereditary and neonatal diseases and abnormalities Huntingtin Protein Huntingtin TOR Serine-Threonine Kinases Autophagy Intracellular Signaling Peptides and Proteins Cellular homeostasis Nerve Tissue Proteins Cell Biology Biology Protein Serine-Threonine Kinases BAG3 Article Cell biology Selective autophagy Drosophila melanogaster mental disorders Cancer research Animals Autophagy-Related Protein-1 Homolog Drosophila Proteins Humans Microtubule-Associated Proteins |
| Zdroj: | Nature cell biology |
| ISSN: | 1476-4679 |
| Popis: | Selective macroautophagy is an important protective mechanism against diverse cellular stresses. In contrast to the well-characterized starvation-induced autophagy, the regulation of selective autophagy is largely unknown. Here, we demonstrate that Huntingtin, the Huntington’s disease gene product, functions as a scaffold protein for selective macroautophagy but it is dispensable for nonselective macroautophagy. In Drosophila, Huntingtin genetically interacts with autophagy pathway components. In mammalian cells, Huntingtin physically interacts with the autophagy cargo receptor p62 to facilitate its association with the integral autophagosome component LC3 and with lysine-63-linked ubiquitin-modified substrates. Maximal activation of selective autophagy during stress is attained by the ability of Huntingtin to bind ULK1, a kinase that initiates autophagy, which releases ULK1 from negative regulation via mTOR. Our data uncover an important physiological function of Huntingtin and provide a missing link in the activation of selective macroautophagy in metazoans. |
| Databáze: | OpenAIRE |
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