Microtubule-Depolymerizing Kinesins in the Regulation of Assembly, Disassembly, and Length of Cilia and Flagella

Hu, Zhangfeng; Liang, Yinwen; Meng, Dan; Wang, Liang; Pan, Junmin

doi:10.1016/bs.ircmb.2015.01.008

Cited by 21 publications

(20 citation statements)

References 126 publications

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“…They can walk on microtubules, but also regulate microtubule length, during mitosis (Gergely, Crapo, Hough, McIntosh, & Betterton, 2016;Grissom et al, 2009;Gupta, Carvalho, Roof, & Pellman, 2006;McHugh, Gluszek, & Welburn, 2018;Savoian & Glover, 2010), and/or ciliary and flagellar assembly (Hu, Liang, Meng, Wang, & Pan, 2015;Niwa et al, 2012;Wang et al, 2016). They can walk on microtubules, but also regulate microtubule length, during mitosis (Gergely, Crapo, Hough, McIntosh, & Betterton, 2016;Grissom et al, 2009;Gupta, Carvalho, Roof, & Pellman, 2006;McHugh, Gluszek, & Welburn, 2018;Savoian & Glover, 2010), and/or ciliary and flagellar assembly (Hu, Liang, Meng, Wang, & Pan, 2015;Niwa et al, 2012;Wang et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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

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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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Section: Introductionmentioning

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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“…The two types of MT-dependent motors, kinesins and dyneins, can both interact with MT ends to affect their dynamics (Hu et al, 2015; Laan et al, 2012; Su et al, 2012; Walczak et al, 2013). Amongst the kinesins, very different modes of regulation of MT polymerization have been reported.…”

Section: Introductionmentioning

confidence: 99%

Kinesin-4 KIF21B is a potent microtubule pausing factor

Riel

Rai

Bianchi

et al. 2017

eLife

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Microtubules are dynamic polymers that in cells can grow, shrink or pause, but the factors that promote pausing are poorly understood. Here, we show that the mammalian kinesin-4 KIF21B is a processive motor that can accumulate at microtubule plus ends and induce pausing. A few KIF21B molecules are sufficient to induce strong growth inhibition of a microtubule plus end in vitro. This property depends on non-motor microtubule-binding domains located in the stalk region and the C-terminal WD40 domain. The WD40-containing KIF21B tail displays preference for a GTP-type over a GDP-type microtubule lattice and contributes to the interaction of KIF21B with microtubule plus ends. KIF21B also contains a motor-inhibiting domain that does not fully block the interaction of the protein with microtubules, but rather enhances its pause-inducing activity by preventing KIF21B detachment from microtubule tips. Thus, KIF21B combines microtubule-binding and regulatory activities that together constitute an autonomous microtubule pausing factor.DOI: http://dx.doi.org/10.7554/eLife.24746.001

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“…The dynein light chain DYNLT1 (Tctex-1) promotes ciliary disassembly before S phase and has been shown to prevent radial glia cells from prematurely exiting the cell cycle in the developing neocortex (Li et al 2011). Several kinesins support ciliary disassembly (Hu et al 2015). The kinesin-13 family member KIF2A has microtubule-depolymerizing properties and is activated by PLK1 (Miyamoto et al 2015); PLK1 is highly expressed during G2/M and plays important roles in centrosome maturation, spindle assembly and cytokinesis (Zitouni et al 2014).…”

Section: Cilia and The Cell Cyclementioning

confidence: 99%

Role of primary cilia in non-dividing and post-mitotic cells

Walz

2017

Cell Tissue Res

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The essential role of primary (non-motile) cilia during the development of multi-cellular tissues and organs is well established and is underlined by severe disease manifestations caused by mutations in cilia-associated molecules that are collectively termed ciliopathies. However, the role of primary cilia in non-dividing and terminally differentiated, post-mitotic cells is less well understood. Although the prevention of cells from re-entering the cell cycle may represent a major chore, primary cilia have recently been linked to DNA damage responses, autophagy and mitochondria. Given this connectivity, primary cilia in non-dividing cells are well positioned to form a signaling hub outside of the nucleus. Such a center could integrate information to initiate responses and to maintain cellular homeostasis if cell survival is jeopardized. These more discrete functions may remain undetected until differentiated cells are confronted with emergencies.

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Microtubule-Depolymerizing Kinesins in the Regulation of Assembly, Disassembly, and Length of Cilia and Flagella

Cited by 21 publications

References 126 publications

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

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

Kinesin-4 KIF21B is a potent microtubule pausing factor

Role of primary cilia in non-dividing and post-mitotic cells

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