TMEM16K is an interorganelle regulator of endosomal sorting

Maja Petkovic (), Juan Oses-Prieto, Alma Burlingame, Lily Yeh Jan and Yuh Nung Jan ()
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Maja Petkovic: University of California at San Francisco
Juan Oses-Prieto: University of California San Francisco
Alma Burlingame: University of California San Francisco
Lily Yeh Jan: University of California at San Francisco
Yuh Nung Jan: University of California at San Francisco

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Communication between organelles is essential for their cellular homeostasis. Neurodegeneration reflects the declining ability of neurons to maintain cellular homeostasis over a lifetime, where the endolysosomal pathway plays a prominent role by regulating protein and lipid sorting and degradation. Here we report that TMEM16K, an endoplasmic reticulum lipid scramblase causative for spinocerebellar ataxia (SCAR10), is an interorganelle regulator of the endolysosomal pathway. We identify endosomal transport as a major functional cluster of TMEM16K in proximity biotinylation proteomics analyses. TMEM16K forms contact sites with endosomes, reconstituting split-GFP with the small GTPase RAB7. Our study further implicates TMEM16K lipid scrambling activity in endosomal sorting at these sites. Loss of TMEM16K function led to impaired endosomal retrograde transport and neuromuscular function, one of the symptoms of SCAR10. Thus, TMEM16K-containing ER-endosome contact sites represent clinically relevant platforms for regulating endosomal sorting.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17016-8

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DOI: 10.1038/s41467-020-17016-8

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