LKB1 destabilizes microtubules in myoblasts and contributes to myoblast differentiation.

PloS One
Isma MianJennifer S Tirnauer

Abstract

Skeletal muscle myoblast differentiation and fusion into multinucleate myotubes is associated with dramatic cytoskeletal changes. We find that microtubules in differentiated myotubes are highly stabilized, but premature microtubule stabilization blocks differentiation. Factors responsible for microtubule destabilization in myoblasts have not been identified. We find that a transient decrease in microtubule stabilization early during myoblast differentiation precedes the ultimate microtubule stabilization seen in differentiated myotubes. We report a role for the serine-threonine kinase LKB1 in both microtubule destabilization and myoblast differentiation. LKB1 overexpression reduced microtubule elongation in a Nocodazole washout assay, and LKB1 RNAi increased it, showing LKB1 destabilizes microtubule assembly in myoblasts. LKB1 levels and activity increased during myoblast differentiation, along with activation of the known LKB1 substrates AMP-activated protein kinase (AMPK) and microtubule affinity regulating kinases (MARKs). LKB1 overexpression accelerated differentiation, whereas RNAi impaired it. Reduced microtubule stability precedes myoblast differentiation and the associated ultimate microtubule stabilization seen in myot...Continue Reading

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Citations

Jun 14, 2014·Proceedings of the National Academy of Sciences of the United States of America·Wenxiang FuBrian David Dynlacht
Dec 15, 2015·Nature Communications·Smitha PillaiSrikumar Chellappan
Oct 13, 2016·Journal of Cellular Physiology·Ziye XuTizhong Shan
Aug 31, 2017·Development·Andrew Muroyama, Terry Lechler
Jan 10, 2017·Journal of Cellular Physiology·Tizhong ShanYizhen Wang
Oct 14, 2018·International Journal of Molecular Sciences·David M Thomson
Oct 21, 2020·Scientific Reports·Cyriel Sebastiaan OlieVered Raz
Jan 2, 2021·International Journal of Biological Macromolecules·Kun ZhangXiaoquan Guo
Feb 10, 2021·Cells·Saline JabreCatherine Coirault

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Methods Mentioned

BETA
gene knockout
transfecting
FCS
scraping

Software Mentioned

MetaMorph

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