Document Detail


Dynein light chain 1 (LC8) association enhances microtubule stability and promotes microtubule bundling.
MedLine Citation:
PMID:  23038268     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Dynein Light Chain 1 (LC8) has been shown to pull down tubulin subunits, suggesting that it interacts with microtubules.
RESULTS: LC8 decorates microtubules in vitro and in Drosophila embryos, promotes microtubule assembly, and stabilizes microtubules both in vitro and in tissue-cultured cells.
CONCLUSION: LC8 stabilizes microtubules.
SIGNIFICANCE: Data provide the first evidence of a novel MAP-like function of LC8. Dynein light chain 1 (LC8), a highly conserved protein, is known to bind to a variety of different polypeptides. It functions as a dimer, which is inactivated through phosphorylation at the Ser-88 residue. A loss of LC8 function causes apoptosis in Drosophila embryos, and its overexpression induces malignant transformation of breast cancer cells. Here we show that LC8 binds to tubulin, promotes microtubule assembly, and induces the bundling of reconstituted microtubules in vitro. Furthermore, LC8 decorates microtubules both in Drosophila embryos and in HeLa cells, increases the microtubule stability, and promotes microtubule bundling in these cells. Microtubule stability influences a number of different cellular functions including mitosis and cell differentiation. The LC8 overexpression reduces the susceptibility of microtubules to cold and nocodazole-induced depolymerization in tissue-cultured cells and increases microtubule acetylation, suggesting that LC8 stabilizes microtubules. We also show that LC8 knockdown or transfection with inhibitory peptides destabilizes microtubules and inhibits bipolar spindle assembly in HeLa cells. In addition, LC8 knockdown leads to the mitotic block in HeLa cells. Furthermore, molecular docking analysis using the crystal structures of tubulin and LC8 dimer indicated that the latter may bind at α-β tubulin junction in a protofilament at sites distinct from the kinesin and dynein binding sites. Together, we provide the first evidence of a novel microtubule-associated protein-like function of LC8 that could explain its reported roles in cellular metastasis and differentiation.
Authors:
Jayant Asthana; Anuradha Kuchibhatla; Swadhin Chandra Jana; Krishanu Ray; Dulal Panda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-04
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-27     Completed Date:  2013-02-28     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  40793-805     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Drosophila / chemistry,  genetics,  metabolism*
Drosophila Proteins / genetics,  metabolism*
Dyneins / genetics,  metabolism*
Kinetics
Microtubules / chemistry,  genetics,  metabolism*
Protein Binding
Chemical
Reg. No./Substance:
0/Drosophila Proteins; 0/ctp protein, Drosophila; EC 3.6.4.2/Dyneins
Comments/Corrections

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