Mechanisms by Which Kinesin-5 Motors Perform Their Multiple Intracellular Functions

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.

CLIC4 is a cytokinetic cleavage furrow protein that regulates cortical cytoskeleton stability during cell division

During mitotic cell division, the actomyosin cytoskeleton undergoes several dynamic changes that play key roles in progression through mitosis. While the regulators of cytokinetic ring formation and contraction are well-established, proteins that regulate cortical stability during anaphase and telophase have been understudied. Here, we describe a role for CLIC4 in regulating actin and actin-regulators at the cortex and cytokinetic cleavage furrow during cytokinesis. We first describe CLIC4 as a new component of the cytokinetic cleavage furrow that is required for successful completion of mitotic cell division. We also demonstrate that CLIC4 regulates the remodeling of sub-plasma membrane actomyosin network within the furrow by recruiting MST4 kinase and regulating ezrin phosphorylation. This work identifies and characterizes new molecular players involved in the transition from the contracting cytokinetic ring to the intercellular bridge during cytokinesis.

Mechanics of cellular packing of nanorods with finite and non-uniform diameters

Theoretical modeling and MD simulations demonstrate that the diameter, length, and shape of an encapsulated nanorod together play key roles in regulating its mechanical interplay with the confining vesicle, shedding light on the cellular packing of microtubule bundles, filopodial protrusion, mitotic cell division, and cytotoxicity.

NEUROPROTECTIVE ROLE OF BIMOCLOMOL IN ECTOPIC CELL CYCLE IN PARKINSON’S DISEASE: NEW INSIGHTS

Objective: Parkinson’s disease (PD) is a debilitating age-related neurodegenerative disease characterized by the canonical formation of intracellular Lewy bodies comprising α-synuclein protein. Despite the knowledge of factors causing PD, it remains irreversible and incurable. Recent studies have highlighted the physiological and pathological involvement of cell cycle proteins in PD. The intriguing relationship between PARK2 and cyclin E which leads to upregulation of cyclin E in the absence of functional PARK2 contributes heavily in the onset and progression of PD. The objective of this study is to explore neuroprotective action of bimoclomol in attenuating the level of cyclin E and inhibiting post-mitotic cell division led neurodegeneration in PD. Methods: We employed various in silico methods such as drug-likeness parameters, namely, Lipinski filter analysis, Ghose parameters, Veber rules, absorption, distribution, metabolism, and excretion - toxicity analysis, pharmacophore based target prediction, active site prediction, and molecular docking studies. Results: The binding of bimoclomol inhibited cyclin E, thereby, attenuating post-mitotic cell division led neurodegeneration in PD. Conclusion: This study outlines the novel potential of bimoclomol in attenuating cyclin E led neuronal death in PD which may be mediated by heat shock proteins (HSP70).