Single-molecule analysis of endogenous β-actin mRNA trafficking reveals a mechanism for compartmentalized mRNA localization in axons.
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Authors
Turner-Bridger, Benita
Jakobs, Maximillian
Wong, Hovy Ho-Wai
Harris, William A
Publication Date
2018-10-09Journal Title
Proc Natl Acad Sci U S A
ISSN
0027-8424
Publisher
Proceedings of the National Academy of Sciences
Volume
115
Issue
41
Pages
E9697-E9706
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Turner-Bridger, B., Jakobs, M., Muresan, L., Wong, H. H., Franze, K., Harris, W. A., & Holt, C. E. (2018). Single-molecule analysis of endogenous β-actin mRNA trafficking reveals a mechanism for compartmentalized mRNA localization in axons.. Proc Natl Acad Sci U S A, 115 (41), E9697-E9706. https://doi.org/10.1073/pnas.1806189115
Abstract
During embryonic nervous system assembly, mRNA localization is precisely regulated in growing axons, affording subcellular autonomy by allowing controlled protein expression in space and time. Different sets of mRNAs exhibit different localization patterns across the axon. However, little is known about how mRNAs move in axons or how these patterns are generated. Here, we couple molecular beacon technology with highly inclined and laminated optical sheet microscopy to image single molecules of identified endogenous mRNA in growing axons. By combining quantitative single-molecule imaging with biophysical motion models, we show that β-actin mRNA travels mainly as single copies and exhibits different motion-type frequencies in different axonal subcompartments. We find that β-actin mRNA density is fourfold enriched in the growth cone central domain compared with the axon shaft and that a modicum of directed transport is vital for delivery of mRNA to the axon tip. Through mathematical modeling we further demonstrate that directional differences in motor-driven mRNA transport speeds are sufficient to generate β-actin mRNA enrichment at the growth cone. Our results provide insight into how mRNAs are trafficked in axons and a mechanism for generating different mRNA densities across axonal subcompartments.
Keywords
Growth Cones, Animals, Xenopus laevis, Actins, Xenopus Proteins, RNA, Messenger, Biological Transport, Active, Models, Biological, Neurogenesis, Molecular Imaging
Sponsorship
Wellcome Trust (085314/Z/08/Z)
European Research Council (322817)
Isaac Newton Trust (Minute 1119(z))
Wellcome Trust (100329/Z/12/Z)
Wellcome Trust (099130/Z/12/Z)
Engineering and Physical Sciences Research Council (EP/R025398/1)
Identifiers
External DOI: https://doi.org/10.1073/pnas.1806189115
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285786
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