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

Shrestha, Sanjay; Hazelbaker, Mark; Yount, Amber L; Walczak, Claire

doi:10.3390/biom9010001

Cited by 22 publications

(15 citation statements)

References 102 publications

(208 reference statements)

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“…This brief report presents some of the biochemical properties of the DdKif10 motor. Previous works in other organisms indicate that Kinesin-8 isoforms are relatively slow, plus-end directed motors, some with distinctive MT depolymerization activities [2]. We show, here, in vitro gliding and ATPase activities, as well as the in vivo localization of a motor fragment.…”

Section: Introductionsupporting

confidence: 64%

“…Kinesin-8 motors are generally considered slow, processive, and accumulate at the MT plus ends where they effect tip dynamics [2]. Our results indicate that the DdKif10 motor domain can move MTs in vitro at about the same rate as the human Kinesin-8 isoform (170 nm/s (Dd) vs. 128-299nm/s (HsKif18A [28])).…”

Section: Discussionmentioning

confidence: 73%

“…The Kinesin-8 family of proteins are microtubule (MT)-based molecular motors that largely function in polymer length control and are required for chromosome alignment, mitotic spindle length determination, and astral MT dynamics in a number of animal and fungal cells [1,2]. Though primarily studied for their mitotic activities, these motors are also known to function during interphase, to facilitate cell polarity, nuclear position, and MT organization [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

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Bioenergetics of the Dictyostelium Kinesin-8 Motor Isoform

Koonce

Tikhonenko

2020

Biomolecules

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The functional organization of microtubules in eukaryotic cells requires a combination of their inherent dynamic properties, interactions with motor machineries, and interactions with accessory proteins to affect growth, shrinkage, stability, and architecture. In most organisms, the Kinesin-8 family of motors play an integral role in these organizations, well known for their mitotic activities in microtubule (MT) length control and kinetochore interactions. In Dictyostelium discoideum, the function of Kinesin-8 remains elusive. We present here some biochemical properties and localization data that indicate that this motor (DdKif10) shares some motility properties with other Kinesin-8s but also illustrates differences in microtubule localization and depolymerase action that highlight functional diversity.

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Section: Introductionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

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Bioenergetics of the Dictyostelium Kinesin-8 Motor Isoform

Koonce

Tikhonenko

2020

Biomolecules

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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%

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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“…Proteomic studies identified 3 kinesins expressed during male gametogenesis (kinesin-8B, -13 and -15)(Khan et al, 2005;Talman et al, 2014), but no functional studies have been conducted until now. 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). Unfortunately, concerning PBANKA_0622400, PBANKA_0609500, PBANKA_0809500, PBANKA_0902400 and PBANKA_1224100, no functional data are available and the number of species possessing orthologues of these proteins is currently very limited, making it difficult to construct any hypothesis concerning their roles.…”

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

Cited by 22 publications

References 102 publications

Bioenergetics of the Dictyostelium Kinesin-8 Motor Isoform

Bioenergetics of the Dictyostelium Kinesin-8 Motor Isoform

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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