Mutation of a gene for a Drosophila kinesin-like protein, Klp38B, leads to failure of cytokinesis

Abstract

Mutations in a gene (Klp38B) encoding a novel kinesin-like protein in Drosophila melanogaster lead to the formation of polyploid cells in the larval central nervous system and in the follicle cells of adult egg chambers. Some homozygous mutants survive to adulthood and also exhibit morphological defects indicative of abnormal cell cycle progression, including rough eyes, missing bristles, and abnormal abdominal cuticles. In larval brains, there is no accumulation of mitotic cells and the frequency of anaphase figures is comparable to wild type, suggesting that nuclear division is not affected. Such brains contain polyploid cells with metaphase and anaphase chromosomes associated with bipolar spindles. Such spindles have a number of unseparated centrosomes at their poles reflecting the degree of polyploidy of the cell. Follicle cells frequently contain two nuclei of roughly equal size. Taken together, we conclude that these Klp38B mutations lead to a failure of cytokinesis resulting in polyploidy, and discuss whether or not this is a direct effect of the mutation.

Autosomal Recessive Primary Microcephaly: Not Just a Small Brain

“…This is supported by several studies conducted in various animal models with depleted KIF14 homologs (Ohkura et al, 1997;Fujikura et al, 2013;Reilly et al, 2019). Mutations of Drosophila KIF14 homolog, also known as kinesin-like protein at 38B (KLP38B), affect the cell cycle progression due to cytokinesis failure (Ohkura et al, 1997). In the same notion, Laggard mice (lag), an animal model for KIF14, are characterized by microcephaly, cortical dysgenesis, and severe hypomyelination as a consequence of massive apoptosis during late neurogenesis (Fujikura et al, 2013).…”

“…It is then unsurprising to realize that mutations in KIF14 also lead to MCPH by a common mechanism as CIT mutations (Moawia et al, 2017;Makrythanasis et al, 2018;Reilly et al, 2019). This is supported by several studies conducted in various animal models with depleted KIF14 homologs (Ohkura et al, 1997;Fujikura et al, 2013;Reilly et al, 2019). Mutations of Drosophila KIF14 homolog, also known as kinesin-like protein at 38B (KLP38B), affect the cell cycle progression due to cytokinesis failure (Ohkura et al, 1997).…”

BUB1/KIF14 complex promotes anaplastic thyroid carcinoma progression by inducing chromosome instability

“…The KIF14 protein belongs to the kinesin subfamily 3 locates on chromosome 1q32.1. It is an essential cytoskeletal protein responsible for cell cycle progression, mitotic spindle formation, cytokinesis completion and chromosomal alignment, segregation and congression 40,64–70 . It has been proved that KIF14 is frequently overexpressed in cancers, which correlates with adverse clinical prognoses, tumour metastases and recurrence 71–77 .…”

“…It is an essential cytoskeletal protein responsible for cell cycle progression, mitotic spindle formation, cytokinesis completion and chromosomal alignment, segregation and congression. 40 , 64 , 65 , 66 , 67 , 68 , 69 , 70 It has been proved that KIF14 is frequently overexpressed in cancers, which correlates with adverse clinical prognoses, tumour metastases and recurrence. 71 , 72 , 73 , 74 , 75 , 76 , 77 Importantly, KIF14 overexpression during tumorigenesis could result in rapid and error‐prone mitosis, thereby causing aneuploidy.…”