期刊
CELL
卷 179, 期 1, 页码 147-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2019.08.050
关键词
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资金
- NINDS, NIH
- Canadian Institutes of Health Research
- Wellcome Trust
- ALS Society of Canada/Brain Canada
- HHMI Janelia Research Campus
Long-distance RNA transport enables local protein synthesis at metabolically-active sites distant from the nucleus. This process ensures an appropriate spatial organization of proteins, vital to polarized cells such as neurons. Here, we present a mechanism for RNA transport in which RNA granules hitchhike on moving lysosomes. In vitro biophysical modeling, live-cell microscopy, and unbiased proximity labeling proteomics reveal that annexin A11 (ANXA11), an RNA granule-associated phosphoinositide-binding protein, acts as a molecular tether between RNA granules and lysosomes. ANXA11 possesses an N-terminal low complexity domain, facilitating its phase separation into membraneless RNA granules, and a C-terminal membrane binding domain, enabling interactions with lysosomes. RNA granule transport requires ANXA11, and amyotrophic lateral sclerosis (ALS)-associated mutations in ANXA11 impair RNA granule transport by disrupting their interactions with lysosomes.Thus, ANXA11 mediates neuronal RNA transport by tethering RNA granules to actively-transported lysomes, performing a critical cellular function that is disrupted in ALS.
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