Human CLEC16A regulates autophagy through modulating mTOR activity

CLEC16A is genetically linked with multiple autoimmune disorders but its functional relevance in autoimmunity remains obscure. Recent evidence has signposted the emerging role of autophagy in autoimmune disease development. Here, by ectopic expression and siRNA silencing, we show that CLEC16A has an...

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Bibliographic Details
Published in:Experimental cell research 2017-03, Vol.352 (2), p.304-312
Main Authors: Tam, Rachel Chun Yee, Li, Michelle Wing Man, Gao, Yan Pan, Pang, Yuen Ting, Yan, Sheng, Ge, Wei, Lau, Chak Sing, Chan, Vera Sau Fong
Format: Article
Language:English
Subjects:
Autophagy
CLEC16A
Confocal microscopy
Cytoplasmic Vesicles - metabolism
Golgi Apparatus - metabolism
HEK293 Cells
HeLa Cells
Humans
Lectins, C-Type - genetics
Lectins, C-Type - metabolism
Monosaccharide Transport Proteins - genetics
Monosaccharide Transport Proteins - metabolism
mTOR signaling
Quantitative proteomics
TOR Serine-Threonine Kinases - metabolism
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Summary:CLEC16A is genetically linked with multiple autoimmune disorders but its functional relevance in autoimmunity remains obscure. Recent evidence has signposted the emerging role of autophagy in autoimmune disease development. Here, by ectopic expression and siRNA silencing, we show that CLEC16A has an inhibitory role in starvation-induced autophagy in human cells. Combining quantitative proteomics and immunoblotting analyses, we found that CLEC16A likely regulates autophagy by activating mTOR pathway. Overexpression of CLEC16A was found to sensitize cells towards the availability of nutrients, resulting in a heightened mTOR activity, which in turn diminished LC3 autophagic activity following nutrient deprivation. CLEC16A deficiency, on the other hand, delayed mTOR activity in response to nutrient sensing, thereby resulted in an augmented autophagic response. CLEC16A was found residing in cytosolic vesicles and the Golgi, and nutrient removal promoted a stronger clustering within the Golgi, where it was possibly in a vantage position to activate mTOR upon nutrient replenishment. These findings suggest that Golgi-associated CLEC16A negatively regulates autophagy via modulation of mTOR activity, and may provide support for a functional link between CLEC16A and autoimmunity.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2017.02.017