Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Dec 20;9(1):1.
doi: 10.3390/biom9010001.

Emerging Insights into the Function of Kinesin-8 Proteins in Microtubule Length Regulation

Sanjay Shrestha  1 , Mark Hazelbaker  2 , Amber L Yount  3 , Claire E Walczak  4
Affiliations
Review

Emerging Insights into the Function of Kinesin-8 Proteins in Microtubule Length Regulation

Sanjay Shrestha et al. Biomolecules. .

Abstract

Proper regulation of microtubules (MTs) is critical for the execution of diverse cellular processes, including mitotic spindle assembly and chromosome segregation. There are a multitude of cellular factors that regulate the dynamicity of MTs and play critical roles in mitosis. Members of the Kinesin-8 family of motor proteins act as MT-destabilizing factors to control MT length in a spatially and temporally regulated manner. In this review, we focus on recent advances in our understanding of the structure and function of the Kinesin-8 motor domain, and the emerging contributions of the C-terminal tail of Kinesin-8 proteins to regulate motor activity and localization.

Keywords: microtubule dynamics; mitosis; molecular motor protein; spindle.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Proposed models for Kinesin-8 MT) depolymerization: (A) The active depolymerization model proposes that the Kinesin-8 motor protein walks on the MT lattice towards the plus end where it dwells for some time before depolymerizing the MT. (B) The capping model proposes that the Kinesin-8 protein, particularly human Kif18A, suppresses MT dynamics at the plus ends by serving as a capping factor. Capping blocks both growth and shrinkage, ultimately leading to MT catastrophe and depolymerization of the MT lattice.
Figure 2
Figure 2
Crystal structures of Kinesin-8 proteins and their cryo-EM MT docked state: (A) Undocked Kif18A complexed with Mg2+-ADP (PDB: 3LRE) [82]. (B) Nucleotide free Kif18A docked to the MT (PDB: 5OAM) [77]. (C) Undocked Kif19A complexed with Mg2+-ADP (PDB: 5GSZ) [79]. (D) Nucleotide free Kif19A docked to the MT (PDB: 5GSY; tubulin coordinates provided by N. Hirokawa) [79]. Key elements required for MT binding and/or MT destabilizing activity are color coded: Switch II cluster (α4-L12-α5) is shown in green, loop L2 in blue, helix α6 in orange, loop L11 in cyan, loop L8 in red, and neck linker (NL) in purple. Helix 12 of α- and β-tubulin is shown in light pink.
Figure 3
Figure 3
Sequence alignment of critical elements of the motor domain associated with MT depolymerization for the Kinesin-13 (Kif2C) and for the Kinesin-8 (Kif19A, Kip3, and Kif18A) proteins. Identical residues are shown in red, similar residues are shown in blue, and dissimilar residues are shown in black. β-sheet residues on either side of loop L2 are included. Clustal W was used for sequence alignment. Accession numbers: mmKif2C NP_608301.3; mmKif19A NP_001096085.1; scKip3 KZV11013.1; hsKif18A NP_112494.3.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Desai A., Mitchison T.J. Microtubule polymerization dynamics. Annu. Rev. Cell Dev. Biol. 1997;13:83–117. doi: 10.1146/annurev.cellbio.13.1.83. - DOI - PubMed
    1. Mitchison T.J. Localization of an exchangeable GTP binding site at the plus end of microtubules. Science. 1993;261:1044–1047. doi: 10.1126/science.8102497. - DOI - PubMed
    1. Weisenberg R.C., Deery W.J., Dickinson P.J. Tubulin-nucleotide interactions during the polymerization and depolymerization of microtubules. Biochemistry. 1976;15:4248–4254. doi: 10.1021/bi00664a018. - DOI - PubMed
    1. Carlier M.F., Pantaloni D. Kinetic analysis of guanosine 5′-triphosphate hydrolysis associated with tubulin polymerization. Biochemistry. 1981;20:1918–1924. doi: 10.1021/bi00510a030. - DOI - PubMed
    1. Mitchison T.J., Kirschner M.W. Dynamic instability of microtubule growth. Nature. 1984;312:237–242. doi: 10.1038/312237a0. - DOI - PubMed

Publication types

LinkOut - more resources