한빛사논문
Abstract
Myungjin Kim, Hae Li Park, Hwan-Woo Park, Seung-Hyun Ro, Samuel G. Nam, John M. Reed, Jun-Lin Guan, Jun Hee Lee*
Myungjin Kim
Department of Molecular and Integrative Physiology; University of Michigan; Ann Arbor, MI USA
These authors contributed equally to this work.
Hae Li Park
Department of Molecular and Integrative Physiology; University of Michigan; Ann Arbor, MI USA
These authors contributed equally to this work.
Hwan-Woo Park
Department of Molecular and Integrative Physiology; University of Michigan; Ann Arbor, MI USA
These authors contributed equally to this work.
Seung-Hyun Ro
Department of Molecular and Integrative Physiology; University of Michigan; Ann Arbor, MI USA
Samuel G. Nam
Department of Molecular and Integrative Physiology; University of Michigan; Ann Arbor, MI USA
John M. Reed
Department of Molecular and Integrative Physiology; University of Michigan; Ann Arbor, MI USA
Jun-Lin Guan
Department of Internal Medicine; University of Michigan; Ann Arbor, MI USA
Jun Hee Lee
*Corresponding author
Department of Molecular and Integrative Physiology; University of Michigan; Ann Arbor, MI USA
Abstract
Autophagy-related 1 (Atg1)/Unc-51-like protein kinases (ULKs) are evolutionarily conserved proteins that play critical physiological roles in controlling autophagy, cell growth and neurodevelopment. RB1-inducible coiled-coil 1 (RB1CC1), also known as PTK2/FAK family-interacting protein of 200 kDa (FIP200) is a recently discovered binding partner of ULK1. Here we isolated the Drosophila RB1CC1/FIP200 homolog (Fip200/CG1347) and showed that it mediates Atg1-induced autophagy as a genetically downstream component in diverse physiological contexts. Fip200 loss-of-function mutants experienced severe mobility loss associated with neuronal autophagy defects and neurodegeneration. The Fip200 mutants were also devoid of both developmental and starvation-induced autophagy in salivary gland and fat body, while having no defects in axonal transport and projection in developing neurons. Interestingly, moderate downregulation of Fip200 accelerated both developmental growth and aging, accompanied by target of rapamycin (Tor) signaling upregulation. These results suggest that Fip200 is a critical downstream component of Atg1 and specifically mediates Atg1’s autophagy-, aging- and growth-regulating functions.
Keywords: Drosophila, aging, autophagy, growth, neurodegeneration
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