PUBLICATION
RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether
- Authors
- Liao, Y.C., Fernandopulle, M.S., Wang, G., Choi, H., Hao, L., Drerup, C.M., Patel, R., Qamar, S., Nixon-Abell, J., Shen, Y., Meadows, W., Vendruscolo, M., Knowles, T.P.J., Nelson, M., Czekalska, M.A., Musteikyte, G., Gachechiladze, M.A., Stephens, C.A., Pasolli, H.A., Forrest, L.R., St George-Hyslop, P., Lippincott-Schwartz, J., Ward, M.E.
- ID
- ZDB-PUB-200609-14
- Date
- 2019
- Source
- Cell 179: 147-164.e20 (Journal)
- Registered Authors
- Drerup, Katie (Catherine)
- Keywords
- ANXA11, Amyotrophic lateral sclerosis, Local translation, Lysosome, Neurodegeneration, Neuron, Organelles contact, Phase separation, RNA granule, RNA transport
- MeSH Terms
-
- Amyotrophic Lateral Sclerosis/metabolism
- Animals
- Animals, Genetically Modified
- Annexins/genetics
- Annexins/metabolism*
- Axonal Transport/physiology*
- Axons/metabolism
- Cell Line, Tumor
- Cytoplasmic Granules/metabolism*
- Female
- Humans
- Induced Pluripotent Stem Cells/metabolism
- Lysosomes/metabolism*
- Male
- Mutation
- Protein Binding
- RNA/metabolism*
- Rats/embryology
- Rats, Sprague-Dawley
- Transfection
- Zebrafish
- PubMed
- 31539493 Full text @ Cell
Citation
Liao, Y.C., Fernandopulle, M.S., Wang, G., Choi, H., Hao, L., Drerup, C.M., Patel, R., Qamar, S., Nixon-Abell, J., Shen, Y., Meadows, W., Vendruscolo, M., Knowles, T.P.J., Nelson, M., Czekalska, M.A., Musteikyte, G., Gachechiladze, M.A., Stephens, C.A., Pasolli, H.A., Forrest, L.R., St George-Hyslop, P., Lippincott-Schwartz, J., Ward, M.E. (2019) RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether. Cell. 179:147-164.e20.
Abstract
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 lysosomes, performing a critical cellular function that is disrupted in ALS.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
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