NIMA-related kinase 1 (NEK1) regulates meiosis I spindle assembly by altering the balance between α-Adducin and Myosin X

Abstract

NIMA-related kinase 1 (NEK1) is a serine/threonine and tyrosine kinase that is highly expressed in mammalian germ cells. Mutations in Nek1 induce anemia, polycystic kidney and infertility. In this study we evaluated the role of NEK1 in meiotic spindle formation in both male and female gametes. Our results show that the lack of NEK1 provokes an abnormal organization of the meiosis I spindle characterized by elongated and/or multipolar spindles, and abnormal chromosome congression. The aberrant spindle structure is concomitant with the disruption in localization and protein levels of myosin X (MYO10) and α-adducin (ADD1), both of which are implicated in the regulation of spindle formation during mitosis. Interaction of ADD1 with MYO10 is dependent on phosphorylation, whereby phosphorylation of ADD1 enables its binding to MYO10 on mitotic spindles. Reduction in ADD1 protein in NEK1 mutant mice is associated with hyperphosphorylation of ADD1, thereby preventing the interaction with MYO10 during meiotic spindle formation. Our results reveal a novel regulatory role for NEK1 in the regulation of spindle architecture and function during meiosis.

Analyses stratified by maternal age and recombination further characterize genes associated with maternal nondisjunction of chromosome 21

“…Finally, rs2560850 in MYO10 is significantly associated in the MII centromeric and MII younger subgroups and attains nominal significance in the MI older and MII older subgroups (Figure 4, maternal MII errors locus #12). In addition to roles in mitotic spindle function and mitotic progression, MYO10 is required for meiotic spindle assembly 51–55 …”

Phosphorylation of Plant Microtubule-Associated Proteins During Cell Division

“…The last family of kinases involved in regulation of mitotic microtubule structures is NEKs. This family of Ser/Thr protein kinases is highly conserved in eukaryotes, where it supervises crucial points in mitosis and cell division (O’Connell et al., 2003; Brieño-Enríquez et al., 2017). In plants, NEKs were shown to regulate cortical microtubules and, in turn, to affect cell expansion, organ growth, and stress responses (Vigneault et al., 2007; Agueci et al., 2012; Takatani et al., 2017).…”

Comprehensive substrate specificity profiling of the human Nek kinome reveals unexpected signaling outputs

“…Notably, the Nek kinase family is not exclusively involved in mitosis, but functionally diverse. Nek kinases have also been reported to play a role in meiosis, ciliary biology, and the response of cells to replication stress and DNA-damage (Figure 1B; Quarmby and Mahjoub, 2005; Melixetian et al, 2009; Moniz and Stambolic, 2011; Choi et al, 2013; Spies et al, 2016; Brieño-Enríquez et al, 2017). The functions of Nek3 and Nek4 are not clear but the current literature suggests that Nek3 may play a role in cell migration (Harrington and Clevenger, 2016), and Nek4 might be involved in regulating microtubule stability (Figure 1B; Doles and Hemann, 2010).…”