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Dynein Light Chain 1 (LC8) Association Enhances Microtubule Stability and Promotes Microtubule Bundling

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Title Dynein Light Chain 1 (LC8) Association Enhances Microtubule Stability and Promotes Microtubule Bundling
 
Creator ASTHANA, J
KUCHIBHATLA, A
JANA, SC
RAY, K
PANDA, D
 
Subject CYTOPLASMIC DYNEIN
FISSION YEAST
IN-VIVO
KINETIC STABILIZATION
DYNAMIC MICROTUBULES
MITOTIC SPINDLE
CROSS-LINKERS
MYOSIN-V
PROTEIN
DROSOPHILA
 
Description 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 alpha-beta 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.
 
Publisher AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
 
Date 2014-10-17T05:30:51Z
2014-10-17T05:30:51Z
2012
 
Type Article
 
Identifier JOURNAL OF BIOLOGICAL CHEMISTRY, 287(48)40793-40805
http://dx.doi.org/10.1074/jbc.M112.394353
http://dspace.library.iitb.ac.in/jspui/handle/100/16072
 
Language en