Single-molecule analysis of endogenous β-actin mRNA trafficking reveals a mechanism for compartmentalized mRNA localization in axons
Turner-Bridger B, Jakobs M, Muresan L, Wong HHW, Franze K, Harris WA, Holt CE (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 115
Pages Range: E9697-E9706
Journal Issue: 41
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 ofmRNA 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.
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APA:
Turner-Bridger, B., Jakobs, M., Muresan, L., Wong, H.H.-W., 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. Proceedings of the National Academy of Sciences of the United States of America, 115(41), E9697-E9706. https://dx.doi.org/10.1073/pnas.1806189115
MLA:
Turner-Bridger, Benita, et al. "Single-molecule analysis of endogenous β-actin mRNA trafficking reveals a mechanism for compartmentalized mRNA localization in axons." Proceedings of the National Academy of Sciences of the United States of America 115.41 (2018): E9697-E9706.
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