Dynein/dynactin is necessary for anterograde transport of Mbp mRNA in oligodendrocytes and for myelination in vivo

Proceedings of the National Academy of Sciences of the United States of America
Amy L HerbertKelly R Monk

Abstract

Oligodendrocytes in the central nervous system produce myelin, a lipid-rich, multilamellar sheath that surrounds axons and promotes the rapid propagation of action potentials. A critical component of myelin is myelin basic protein (MBP), expression of which requires anterograde mRNA transport followed by local translation at the developing myelin sheath. Although the anterograde motor kinesin KIF1B is involved in mbp mRNA transport in zebrafish, it is not entirely clear how mbp transport is regulated. From a forward genetic screen for myelination defects in zebrafish, we identified a mutation in actr10, which encodes the Arp11 subunit of dynactin, a critical activator of the retrograde motor dynein. Both the actr10 mutation and pharmacological dynein inhibition in zebrafish result in failure to properly distribute mbp mRNA in oligodendrocytes, indicating a paradoxical role for the retrograde dynein/dynactin complex in anterograde mbp mRNA transport. To address the molecular mechanism underlying this observation, we biochemically isolated reporter-tagged Mbp mRNA granules from primary cultured mammalian oligodendrocytes to show that they indeed associate with the retrograde motor complex. Next, we used live-cell imaging to show ...Continue Reading

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Citations

May 14, 2018·FEBS Letters·Allison M GickingWeihong Qiu
May 18, 2018·Scientific Reports·Shoko ShimizuShingo Miyata
Aug 10, 2018·Neural Development·Rebecca L CunninghamKelly R Monk
Sep 9, 2020·Nature Neuroscience·Jiakun ChenKelly R Monk
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Apr 24, 2020·Developmental Neurobiology·Maya WeigelMeng-Meng Fu
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Dec 17, 2021·Frontiers in Cell and Developmental Biology·Sarah A Neely, David A Lyons

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Methods Mentioned

BETA
transmission electron microscopy
transgenic
genotyping
confocal microscopy
immunoprecipitation
immunoprecipitations
sumoylation
restriction digest
PCR
Assay

Software Mentioned

FIJI
DanioVision
RStudio
GraphPad Prism
Kymograph
R

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