The minibrain kinase homolog, mbk-2, is required for spindle positioning and asymmetric cell division in early C. elegans embryos

Abstract

In the newly fertilized Caenorhabditis elegans zygote, cytoplasmic determinants become localized asymmetrically along the anterior-posterior (A-P) axis of the embryo. The mitotic apparatus then orients so as to cleave the embryo into anterior and posterior blastomeres that differ in both size and developmental potential. Here we describe a role for MBK-2, a member of the Dyrk family of protein kinases, in asymmetric cell division in C. elegans. In mbk-2 mutants, the initial mitotic spindle is misplaced and cytoplasmic factors, including the germline-specific protein PIE-1, are mislocalized. Our findings support a model in which MBK-2 down-regulates the katanin-related protein MEI-1 to control spindle positioning and acts through distinct, as yet unknown factors, to control the localization of cytoplasmic determinants. These findings in conjunction with work from Schizosaccharomyces pombe indicate a possible conserved role for Dyrk family kinases in the regulation of spindle placement during cell division.

Levels of the ubiquitin ligase substrate adaptor MEL-26 are inversely correlated with MEI-1/katanin microtubule-severing activity during both meiosis and mitosis

“…Substrates are often phosphorylated prior to ubiquitination (Glickman and Ciechanover, 2002; Hunter, 2007; Petroski and Deshaies, 2005), and phosphorylation of MEI-1 by the DYRK minibrain kinase MBK-2 is required for timely degradation of MEI-1 (Ming Pang et al, 2004; Pellettieri et al, 2003; Quintin et al, 2003; Stitzel et al, 2006). MBK-2 has additional targets in the oocyte, including the OMA-1/OMA-2 and MEX-5/MEX-6 proteins and components of the germ plasm (DeRenzo et al, 2003; Feng et al, 1999; Nishi and Lin, 2005; Shirayama et al, 2006; Stitzel et al, 2006).…”

Dyrk kinases regulate phosphorylation of doublecortin, cytoskeletal organization, and neuronal morphology

“…The morphological effects of Dyrk proteins in neurons suggest effects on the neuronal cytoskeleton, and Dyrks are known to regulate cytoskeletal dynamics (Pang et al, 2004; Cole et al, 2006; Tatebe et al, 2008; Maddika and Chen, 2009). We began to investigate this issue by examining the distribution of tubulin, F-actin, and DCX (a microtubule-binding protein enriched in the tips of growing neurites (Schaar et al, 2004)), in neurons expressing each of the four Dyrks.…”

“…Dyrk1A can affect cytoskeletal organization through its role as a priming kinase for GSK3β on MAP1b (Scales et al, 2009), but it is mainly the Dyrk2/3 family that has been implicated in MT dynamics. A yeast ortholog (Pom1) is involved in translation of MT-dependent polarity cues into actin filament formation (Tatebe et al, 2008), and an ortholog in C. elegans (Mbk-2) regulates an E3 ubiquitin ligase responsible for the degradation of the MT-severing protein MEI-1/katanin (Pang et al, 2004). In mammals, Dyrk2 is involved in a related E3 pathway for katanin degradation (Maddika and Chen, 2009), and also acts as a priming kinase for GSK3β in the phosphorylation and regulation of the MT binding protein CRMP4 (Cole et al, 2006).…”

The Genetics and Cell Biology of Fertilization

“…MBK-2 helps regulate early embryonic development after fertilization by phosphorylating maternal substrates for degradation. These MBK-2 targets include the katanin subunit MEI-1, the RNA/TAF-4 binding proteins OMA-1 and OMA-2, and the polarity factors MEX-5 and MEX-6 (Detwiler, Reuben et al 2001; Pellettieri, Reinke et al 2003; Quintin, Mains et al 2003; Pang, Ishidate et al 2004; Nishi and Lin 2005; Guven-Ozkan, Nishi et al 2008). Appropriate GFP strains can be used to assess whether other egg activation mutants exhibit defects in the localization, sorting, or degradation of any of these known components.…”