Role and regulation of kinesin-8 motors through the cell cycle

Millar, Jonathan

doi:10.1007/s11693-014-9140-z

Cited by 22 publications

(33 citation statements)

References 86 publications

(112 reference statements)

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“…Kinesin‐8 proteins are motor proteins associated with microtubule dynamics . The loss of Kinesin‐8 proteins in the process of cell division is correlated with disordered mitotic chromosome movement and chromosome loss .…”

Section: Discussionmentioning

confidence: 90%

Kinesin family member 18B: A contributor and facilitator in the proliferation and metastasis of cutaneous melanoma

Yan

Zhu

Zhang

2019

J Biochem & Molecular Tox

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Melanoma is the most aggressive type of cutaneous tumor and the occurrence of metastasis makes it resistant to almost all available treatment and becomes incorrigible. Hence, identifying metastasis‐related biomarkers and effective therapeutic targets will assist in preventing metastasis and ameliorating cutaneous melanoma. In our present study, we reported kinesin family member 18B (KIF18B) as a novel contributor in cutaneous melanoma proliferation and metastasis, and it was found to be of great significance in predicting the prognosis of cutaneous melanoma patients. Bioinformatics analysis based on ONCOMINE, The Cancer Genome Atlas, and Genotype‐Tissue Expression database revealed that KIF18B was highly expressed in cutaneous melanoma and remarkably correlated with unfavorable clinical outcomes. Consistently, the results of the quantitative real‐time polymerase chain reaction exhibited that the expression of KIF18B was significantly higher in cutaneous melanoma cell lines than that in normal cells. In vitro, biological assays found that knockdown of KIF18B in cutaneous melanoma cells noticeably repressed cell proliferation, migration, and invasion, while inducing cell apoptosis. Moreover, the protein expression of E‐cadherin was enhanced while the expression of N‐cadherin, vimentin, and Snail was decreased in M14 cells after knocking down KIF18B. In addition, the phosphorylation of phosphoinositide 3‐kinase (PI3K) and extracellular‐signal‐regulated kinase (ERK) was significantly suppressed in M14 cells with silenced KIF18B. Above all, our results indicated that the repression of cutaneous melanoma cell migration and proliferation caused by KIF18B depletion suggested an oncogenic role of KIF18B in cutaneous melanoma, which acts through modulating epithelial‐mesenchymal transition and ERK/PI3K pathway.

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Section: Discussionmentioning

confidence: 90%

Kinesin family member 18B: A contributor and facilitator in the proliferation and metastasis of cutaneous melanoma

Yan

Zhu

Zhang

2019

J Biochem & Molecular Tox

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“…The importance of Kinesin-8 molecular motors in mitosis in many eukaryotes is wellestablished. These motors move on spindle MTs towards their plus end and regulate spindle dynamics, contributing to spindle length and positioning, and thus to chromosome alignment during metaphase [44][45][46]. Although the exact molecular basis of these functions remains controversial, Kinesin-8s modulate MT dynamics and may either stabilise, destabilise, slow growth, or actively depolymerize MTs in spindle function [18,19,47].…”

Section: Discussionmentioning

confidence: 99%

“…Only Kinesin-8X and Kinesin-13 are found throughout all investigated Apicomplexa. This observation could either reflect a high level of sequence diversity among Kinesin proteins,or underline the plasticity of Kinesin functions during the evolution of Apicomplexa genomes.Protein sequence analysis of PbKinesin-8X, and its orthologue PfKinesin-8X, identified the conserved kinesin motor domain in the middle of the protein, in contrast to its N-terminal location in Kinesin-8s of most other organisms[44]. Nevertheless, expressed recombinant motor domains had MT-dependent gliding activity, like that of other Kinesin-8 motor domains, albeit slower than human Kinesin-8 Kif18A[38].…”

mentioning

confidence: 95%

Plasmodium Kinesin-8X associates with mitotic spindles and is essential for oocyst development during parasite proliferation and transmission

Zeeshan

Shilliday

Liu

et al. 2019

Preprint

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Kinesin-8 proteins are microtubule motors that are often involved in regulation of mitotic spindle length and chromosome alignment. They move towards the ends of spindle microtubules and regulate the dynamics of these ends due, at least in some species, to their microtubule depolymerization activity. Plasmodium spp. exhibit an atypical endomitotic cell division in which chromosome condensation and spindle dynamics are not well understood in the different proliferative stages. Genome-wide homology analysis of Plasmodium spp. revealed the presence of two Kinesin-8 motor proteins (Kinesin-8X and Kinesin-8B). Here we have studied the biochemical properties of Kinesin-8X and its role in parasite proliferation. In vitro, Kinesin-8X showed motile and depolymerization activities like other Kinesin-8 motors. To understand its role in cell division, we have used protein tagging and live cell imaging to define the location of Plasmodium Kinesin-8X during all proliferative stages of the P berghei life cycle. Furthermore, we have used gene targeting to analyse the function of Kinesin-8X. The results reveal a spatio-temporal involvement of Kinesin-8X in spindle dynamics and its association with both mitotic and meiotic spindles and the putative microtubule organising centre (MTOC). Deletion of the Kinesin-8X gene showed that this protein is required for endomitotic division during oocyst development and is therefore necessary for parasite replication within the mosquito gut, and for transmission to the vertebrate host. Consistently, transcriptome analysis of Δkinesin-8X parasites reveals modulated expression of genes involved mainly in microtubulebased processes, chromosome organisation and the regulation of gene expression supporting a role in cell division. 4 Author SummaryKinesins are microtubule-based motors that play key roles in intracellular transport, cell division and motility. Members of the Kinesin-8 family contribute to chromosome alignment during cell division in many eukaryotes. However, the roles of kinesins in the atypical cell division in Plasmodium, the causative agent of malaria, is not known.In contrast to many other eukaryotes, Plasmodium proliferates by endomitosis, in which genome replication and division occur within a nucleus bounded by a persistent nuclear envelope. We show that the Plasmodium genome encodes only nine kinesins and we further investigate the role of Kinesin-8X throughout the Plasmodium life cycle using biochemical and gene targeting approaches. We show that Plasmodium Kinesin-8X has microtubule-based motility and depolymerization activity. We also show that Kinesin-8X is probably localized on putative MTOCs and spindles during cell division in most of the stages of P. berghei life cycle. By gene deletion we demonstrate that Kinesin-8X is essential for normal oocyst development and sporozoite formation. Genome-wide RNA analysis of Δkinesin-8X parasites reveals modulated expression of genes involved in microtubule-based processes. Overall, the data suggest that Kinesin-8X is a molecular ...

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“…According to two transcriptomic studies, all kinesin encoding genes in P. berghei are expressed during the sexual stage Yeoh et al, 2017) In other eukaryotes, kinesin-8 family members, which share a family-specific helical neck region (Miki, Okada, & Hirokawa, 2005), have been shown to be involved in both mitosis and microtubule regulation in cilia/flagella. The members of the kinesin-8A subfamily are found in different organisms and their roles in mitosis, often promoting microtubule catastrophe, have been studied extensively (Dave et al, 2018;Edzuka & Goshima, 2019;Gergely et al, 2016;Grissom et al, 2009;Messin & Millar, 2014;Savoian & Glover, 2010;Su et al, 2013). In fission yeast, additional roles involving cell polarity and control of cortical microtubule length have been shown (Meadows et al, 2018;West, Malmstrom, Troxell, & McIntosh, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…In other eukaryotes, orthologues for kinesin-4,-5, -8B, -13 and -15 are known to be involved in microtubule dynamics and particularly mitosis and cilia/flagella length regulation (Almeida & Maiato, 2018; Hu et al, 2015; Ma, Wang, & Yang, 2017; Muhia et al, 2016; Niwa, 2015; Niwa et al, 2012; Shrestha, Hazelbaker, Yount, & Walczak, 2018; Singh, Pandey, Al-Bassam, & Gheber, 2018; van Riel et al, 2017). The members of the kinesin-8A subfamily are found in different organisms and their roles in mitosis, often promoting microtubule catastrophe, have been studied extensively(Dave et al, 2018;Edzuka & Goshima, 2019;Gergely et al, 2016;Grissom et al, 2009;Messin & Millar, 2014;Savoian & Glover, 2010;Su et al, 2013). The members of the kinesin-8A subfamily are found in different organisms and their roles in mitosis, often promoting microtubule catastrophe, have been studied extensively(Dave et al, 2018;Edzuka & Goshima, 2019;Gergely et al, 2016;Grissom et al, 2009;Messin & Millar, 2014;Savoian & Glover, 2010;Su et al, 2013).…”

mentioning

confidence: 99%

Vital role forPlasmodium bergheiKinesin8B in axoneme assembly during male gamete formation and mosquito transmission

Depoix

Marques

Ferguson

et al. 2019

Cellular Microbiology

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Sexual development is an essential phase in the Plasmodium life cycle, where male gametogenesis is an unusual and extraordinarily rapid process. It produces 8 haploid motile microgametes, from a microgametocyte within 15 minutes. Its unique achievement lies in linking the assembly of 8 axonemes in the cytoplasm to the three rounds of intranuclear genome replication, forming motile microgametes, which are expelled in a process called exflagellation. Surprisingly little is known about the actors involved in these processes. We are interested in kinesins, molecular motors that could play potential roles in male gametogenesis. We have undertaken a functional characterization in Plasmodium berghei of kinesin-8B (PbKIN8B) expressed specifically in male gametocytes and gametes. By generating Pbkin8B-gfp parasites, we show that PbKIN8B is specifically expressed during male gametogenesis and is associated with the axoneme. We created a ΔPbkin8B knockout cell line and analysed the consequences of the absence of PbKIN8B on male gametogenesis. We show that the ability to produce sexually differentiated gametocytes is not affected in ΔPbkin8B parasites and that the 3 rounds of genome replication occur normally. Nevertheless, the development to free motile microgametes is halted and the life cycle is interrupted in vivo. Ultrastructural analysis revealed that intranuclear mitoses are unaffected whereas cytoplasmic microtubules, although assembled in doublets and elongated, fail to assemble in the normal axonemal '9+2' structure and become motile. Absence of a functional axoneme prevented microgamete assembly and release from the microgametocyte, severely reducing infection of the mosquito vector. This is the first functional study of a kinesin involved in male gametogenesis.These results reveal a previously unknown role for PbKIN8B in male gametogenesis, providing new insights into Plasmodium flagellar formation.

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Role and regulation of kinesin-8 motors through the cell cycle

Cited by 22 publications

References 86 publications

Kinesin family member 18B: A contributor and facilitator in the proliferation and metastasis of cutaneous melanoma

Kinesin family member 18B: A contributor and facilitator in the proliferation and metastasis of cutaneous melanoma

Plasmodium Kinesin-8X associates with mitotic spindles and is essential for oocyst development during parasite proliferation and transmission

Vital role forPlasmodium bergheiKinesin8B in axoneme assembly during male gamete formation and mosquito transmission

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