Bipolar kinesin-5 motor proteins perform multiple intracellular functions, mainly during mitotic cell division. Their specialized structural characteristics enable these motors to perform their essential functions by crosslinking and sliding apart antiparallel microtubules (MTs). In this review, we discuss the specialized structural features of kinesin-5 motors, and the mechanisms by which these features relate to kinesin-5 functions and motile properties. In addition, we discuss the multiple roles of the kinesin-5 motors in dividing as well as in non-dividing cells, and examine their roles in pathogenetic conditions. We describe the recently discovered bidirectional motility in fungi kinesin-5 motors, and discuss its possible physiological relevance. Finally, we also focus on the multiple mechanisms of regulation of these unique motor proteins.
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http://dx.doi.org/10.3390/ijms22126420 | DOI Listing |
Curr Biol
January 2025
Department of Cell Biology, Duke University Medical Center, Durham, NC 27705, USA; Duke Center for Quantitative Living Systems, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:
Anaphase is tightly controlled spatiotemporally to ensure proper separation of chromosomes. The mitotic spindle, the self-organized microtubule structure driving chromosome segregation, scales in size with the available cytoplasm. Yet, the relationship between spindle size and chromosome movement remains poorly understood.
View Article and Find Full Text PDFJ Cell Biol
March 2025
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
The tubulin code hypothesis predicts that tubulin tails create programs for selective regulation of microtubule-binding proteins, including kinesin motors. However, the molecular mechanisms that determine selective regulation and their relevance in cells are poorly understood. We report selective regulation of budding yeast kinesin-5 motors by the β-tubulin tail.
View Article and Find Full Text PDFNeurobiol Dis
January 2025
Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam and VU Medical Center, Amsterdam, the Netherlands; Department of Human Genetics, Amsterdam University Medical Center, Amsterdam, the Netherlands. Electronic address:
Mutations in the microtubule-binding motor protein kinesin 5 A (KIF5A) are implicated in several adult-onset motor neuron diseases, including Amyotrophic Lateral Sclerosis, Spastic Paraplegia Type 10 and Charcot-Marie-Tooth Disease Type 2. While KIF5 family members transport a variety of cargos along axons, the specific cargos affected by KIF5A mutations remain poorly understood. Here, we generated KIF5Anull mutant human motor neurons and analyzed the impact on axonal transport and motor neuron outgrowth and regeneration in vitro.
View Article and Find Full Text PDFMethods Mol Biol
November 2024
Laboratory of Molecular and Chemical Cell Biology, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, Japan.
Kinesin-5 motor proteins are essential for mitotic spindle formation and maintenance, ensuring accurate chromosome segregation. Human kinesin-5 is highly expressed in various cancer cells but not in nonproliferative tissues; therefore, it is expected to be an attractive target for cancer chemotherapy, with fewer adverse side effects. Many inhibitors have been developed and subjected to clinical trials; however, they have not yet been commercially distributed because of their poor efficacy and frequent drug resistance.
View Article and Find Full Text PDFCurr Biol
October 2024
Department of Physics, University of Colorado Boulder, Colorado Avenue, Boulder, CO 80309, USA; Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Colorado Avenue, Boulder, CO 80309, USA. Electronic address:
Kinesin-5 motors play an essential role during mitotic spindle assembly in many organisms: they crosslink antiparallel spindle microtubules, step toward plus ends, and slide the microtubules apart. This activity separates the spindle poles and chromosomes. Kinesin-5s are not only plus-end-directed but can walk or be carried toward MT minus ends, where they show enhanced localization.
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