Bidirectional motility of kinesin-5 motor proteins: structural determinants, cumulative functions and physiological roles

Abstract

Mitotic kinesin-5 bipolar motor proteins perform essential functions in mitotic spindle dynamics by crosslinking and sliding antiparallel microtubules (MTs) apart within the mitotic spindle. Two recent studies have indicated that single molecules of Cin8, the Saccharomyces cerevisiae kinesin-5 homolog, are minus end-directed when moving on single MTs, yet switch directionality under certain experimental conditions (Gerson-Gurwitz et al., EMBO J 30:4942-4954, 2011; Roostalu et al., Science 332:94-99, 2011). This finding was unexpected since the Cin8 catalytic motor domain is located at the N-terminus of the protein, and such kinesins have been previously thought to be exclusively plus end-directed. In addition, the essential intracellular functions of kinesin-5 motors in separating spindle poles during mitosis can only be accomplished by plus end-directed motility during antiparallel sliding of the spindle MTs. Thus, the mechanism and possible physiological role of the minus end-directed motility of kinesin-5 motors remain unclear. Experimental and theoretical studies from several laboratories in recent years have identified additional kinesin-5 motors that are bidirectional, revealed structural determinants that regulate directionality, examined the possible mechanisms involved and have proposed physiological roles for the minus end-directed motility of kinesin-5 motors. Here, we summarize our current understanding of the remarkable ability of certain kinesin-5 motors to switch directionality when moving along MTs.

Kinesin-6 Klp9 plays motor-dependent and -independent roles in collaboration with Kinesin-5 Cut7 and the microtubule crosslinker Ase1 in fission yeast

“…Recently, it has become clear that fungal Kinesin-5s including Cut7 are bidirectional motors; they display either plus end-directed or minus end-directed motilities depending upon conditions (eg. the degree of motor crowding on the microtubule lattice) [59][60][61] . Under our experimental conditions, we did not detect a similar bi-directionality, despite Klp9 forming homotetramers like Cut7.…”

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

“…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.…”

DNA damage in telophase leads to coalescence between segregated sister chromatid loci

“…These results led us to check the behaviour of Cin8 upon DNA damage in telophase. Cin8 is a bidirectional mitotic kinesin-5 motor that slide away antiparallel interpolar microtubules, thus favouring spindle elongation in anaphase (Khmelinskii et al 2009;Singh et al 2018). Upon phleomycin treatment, Cin8 relocated from the spindle to two discrete foci in telophase-blocked cells (Fig 3d).…”

“…Consequently, a partial dephosphorylation of Cin8 occurs upon DNA damage in telophase. We hypothesize that this Cin8 relocalization is likely a consequence of its novel minus-end-directed motility (Singh et al 2018), and might reset the spindle to revert its elongation in cells already in late-anaphase.…”