KIF15 explained

Kinesin family member 15 is a protein that in humans is encoded by the KIF15 gene.^[1]

This gene encodes a motor protein that is part of the kinesin superfamily. KIF15 maintains half spindle separation by opposing forces generated by other motor proteins. KIF15 co-localizes with microtubules and actin filaments in both dividing cells and in postmitotic neurons.^[1]

Function

KIF15 (also known as Kinesin-12 and HKLP2) is a motor protein expressed in all cells during mitosis and in postmitotic neurons undergoing axon growth.^[2] KIF15 maintains bipolar microtubule spindle apparatus in dividing cells and shares redundant functions with KIF11.^[3] KIF15 is thought to promote spindle assembly by cross-linking and sliding along microtubules creating a separation between centrosomes. The microtubule localization of Kif15 is being regulated by Kinesin binding protein (KBP).^[4] HeLa cells depleted of KIF11, with reduced microtubule dynamics, are able to form bipolar spindles from acentrosomal asters in a KIF15 dependent manner.^{[5] [6]} Hence, inhibition of KIF15 function will be a vital therapeutic approach in cancer chemotherapy.^[7] Since KIF11 and KIF15 are functionally redundant, drugs targeting both the proteins will be more potent.

Function in neurons

KIF15 restricts the movement of short microtubules into growing axons by generating forces on microtubules which counteract those generated by cytoplasmic dynein.^{[8] [9]} KIF15, together with KIF23 become enriched in dendrites as neurons mature to promote the transport of minus-end distal microtubules into nascent dendrites.^[8]

Interactions

KIF15 has been shown to interact with TPX2. Both these dimers cooperate to slide along microtubules and maintain bipolar spindles.^{[10] [11]}

Further reading

• Courtois A, Schuh M, Ellenberg J, Hiiragi T . The transition from meiotic to mitotic spindle assembly is gradual during early mammalian development . The Journal of Cell Biology . 198 . 3 . 357–70 . August 2012 . 22851319 . 3413348 . 10.1083/jcb.201202135 .
• Oh SA, Allen T, Kim GJ, Sidorova A, Borg M, Park SK, Twell D . Arabidopsis Fused kinase and the Kinesin-12 subfamily constitute a signalling module required for phragmoplast expansion . The Plant Journal . 72 . 2 . 308–19 . October 2012 . 22709276 . 10.1111/j.1365-313X.2012.05077.x . free .
• Dumont J . Bipolar disorder: kinesin-12 to the rescue . Cell Cycle . 11 . 2 . 212–3 . January 2012 . 22214669 . 10.4161/cc.11.2.18785 . free .
• Goshima G . Identification of a TPX2-like microtubule-associated protein in Drosophila . PLOS ONE . 6 . 11 . e28120 . 2011 . 22140519 . 3227607 . 10.1371/journal.pone.0028120 . 2011PLoSO...628120G . free .
• Ho CM, Hotta T, Guo F, Roberson RW, Lee YR, Liu B . Interaction of antiparallel microtubules in the phragmoplast is mediated by the microtubule-associated protein MAP65-3 in Arabidopsis . The Plant Cell . 23 . 8 . 2909–23 . August 2011 . 21873565 . 3180800 . 10.1105/tpc.110.078204 .
• Liu M, Nadar VC, Kozielski F, Kozlowska M, Yu W, Baas PW . Kinesin-12, a mitotic microtubule-associated motor protein, impacts axonal growth, navigation, and branching . The Journal of Neuroscience . 30 . 44 . 14896–906 . November 2010 . 21048148 . 3064264 . 10.1523/JNEUROSCI.3739-10.2010 .
• Gong Y, Ma Z, Patel V, Fischer E, Hiesberger T, Pontoglio M, Igarashi P . HNF-1beta regulates transcription of the PKD modifier gene Kif12 . Journal of the American Society of Nephrology . 20 . 1 . 41–7 . January 2009 . 19005009 . 2615735 . 10.1681/ASN.2008020238 .
• Lee YR, Li Y, Liu B . Two Arabidopsis phragmoplast-associated kinesins play a critical role in cytokinesis during male gametogenesis . The Plant Cell . 19 . 8 . 2595–605 . August 2007 . 17720869 . 2002617 . 10.1105/tpc.107.050716 .
• Müller S, Han S, Smith LG . Two kinesins are involved in the spatial control of cytokinesis in Arabidopsis thaliana . Current Biology . 16 . 9 . 888–94 . May 2006 . 16682350 . 10.1016/j.cub.2006.03.034 . free . 2006CBio...16..888M .

External links

• Web site: Research of Thomas Mayer . University of Konstanz . 2012-12-30 . https://web.archive.org/web/20130203000030/http://www.uni-konstanz.de/thomasmayer/research.html . 2013-02-03 . dead .

Notes and References

1. Web site: Entrez Gene: Kinesin family member 15 .
2. Buster DW, Baird DH, Yu W, Solowska JM, Chauvière M, Mazurek A, Kress M, Baas PW . Expression of the mitotic kinesin Kif15 in postmitotic neurons: implications for neuronal migration and development . Journal of Neurocytology . 32 . 1 . 79–96 . January 2003 . 14618103 . 10.1023/a:1027332432740 . 6734564 .
3. Vanneste D, Takagi M, Imamoto N, Vernos I . The role of Hklp2 in the stabilization and maintenance of spindle bipolarity . Current Biology . 19 . 20 . 1712–7 . November 2009 . 19818619 . 10.1016/j.cub.2009.09.019 . free . 2009CBio...19.1712V .
4. Sebastian J, Rathinasamy K . Benserazide Perturbs Kif15-kinesin Binding Protein Interaction with Prolonged Metaphase and Defects in Chromosomal Congression: A Study Based on in silico Modeling and Cell Culture . Molecular Informatics . minf.201900035 . July 2019 . 39 . 3 . 31347789 . 10.1002/minf.201900035 . 198911009 .
5. Florian S, Mayer TU . Modulated microtubule dynamics enable Hklp2/Kif15 to assemble bipolar spindles . Cell Cycle . 10 . 20 . 3533–44 . October 2011 . 22024925 . 10.4161/cc.10.20.17817 . free .
6. Dumont J . Bipolar disorder: kinesin-12 to the rescue . Cell Cycle . 11 . 2 . 212–3 . January 2012 . 22214669 . 10.4161/cc.11.2.18785 . free .
7. Sebastian J . Dihydropyrazole and dihydropyrrole structures based design of Kif15 inhibitors as novel therapeutic agents for cancer . Computational Biology and Chemistry . 68 . 164–174 . June 2017 . 28355588 . 10.1016/j.compbiolchem.2017.03.006 .
8. Lin S, Liu M, Mozgova OI, Yu W, Baas PW . Mitotic motors coregulate microtubule patterns in axons and dendrites . The Journal of Neuroscience . 32 . 40 . 14033–49 . October 2012 . 23035110 . 3482493 . 10.1523/JNEUROSCI.3070-12.2012 .
9. Liu M, Nadar VC, Kozielski F, Kozlowska M, Yu W, Baas PW . Kinesin-12, a mitotic microtubule-associated motor protein, impacts axonal growth, navigation, and branching . The Journal of Neuroscience . 30 . 44 . 14896–906 . November 2010 . 21048148 . 3064264 . 10.1523/JNEUROSCI.3739-10.2010 .
10. Tanenbaum ME, Macůrek L, Janssen A, Geers EF, Alvarez-Fernández M, Medema RH . Kif15 cooperates with eg5 to promote bipolar spindle assembly . Current Biology . 19 . 20 . 1703–11 . November 2009 . 19818618 . 10.1016/j.cub.2009.08.027 . 15875832 . free . 2009CBio...19.1703T .
11. Vanneste D, Ferreira V, Vernos I . Chromokinesins: localization-dependent functions and regulation during cell division . Biochemical Society Transactions . 39 . 5 . 1154–60 . October 2011 . 21936781 . 10.1042/BST0391154 .