Schizosaccharomyces pombe NIMA-related kinase, Fin1, regulates spindle formation and an affinity of Polo for the SPB

Abstract

The Aspergillus nidulans protein kinase NIMA regulates mitotic commitment, while the human and Xenopus equivalents in¯uence centrosome function. Two recessive, temperature-sensitive mutations in the Schizosaccharomyces pombe NIMA homologue, Fin1, blocked spindle formation at 37°C. One of the two spindle pole bodies (SPBs) failed to nucleate microtubules. This phenotype was reduced by accelerating mitotic commitment through genetic inhibition of Wee1 or activation of either Cdc25 or Cdc2. Polo kinase (Plo1) normally associates with the SPB of mitotic, but not interphase cells. cut12.s11 is a dominant mutation in an SPB component that both suppresses cdc25 mutants and promotes Plo1 association with the interphase SPB. Both cut12.s11 phenotypes were abolished by removing Fin1 function. Elevating Fin1 levels promoted Plo1 recruitment to the interphase SPB of wild-type cells and reduced the severity of the cdc25.22 phenotype. These data are consistent with Fin1 regulating Plo1 function during mitotic commitment. The ®n1 mitotic commitment and spindle phenotypes resemble distinct nimA phenotypes in different systems and suggest that the function of this family of kinases may be conserved across species.

TINA Interacts with the NIMA Kinase inAspergillus nidulansand Negatively Regulates Astral Microtubules during Metaphase Arrest

“…Additionally, forcing cells into mitosis without normal NIMA activity by mutation of the bimE APC/C component causes marked mitotic defects with SPBs unable to nucleate normal bipolar spindles in the absence of fully active NIMA (Osmani et al, 1991b). Data from other systems also support a role for NIMA-related kinases in spindle formation (Grallert and Hagan, 2002;Krien et al, 2002). The current work indicates a potential role for the NIMA interacting protein TINA in astral microtubule formation during mitosis.…”

“…Although NIMA is essential for mitotic progression in A. nidulans (Ye et al, 1998) the NIMA-like Fin1p kinase of S. pombe is nonessential (Grallert and Hagan, 2002;Krien et al, 1998) but does play a role in mitotic regulation (Krien et al, 2002). Fin1p has therefore been proposed to play a fine-tuning role for mitotic progression and TINA could also be involved in such fine-tuning nonessential mitotic functions.…”

“…Stable versions of NIMA prevent normal exit from mitosis . The mitotic promoting activity of NIMA crosses species barriers from yeast to humans (Lu and Hunter, 1995a), indicating conserved NIMA substrates are involved in mitotic regulation.NIMA-related kinases have been isolated from Neurospora crassa and Schizosaccharomyces pombe (Krien et al, 1998), and the S. pombe NIMA-like kinase Fin1p is involved in mitotic regulation (Grallert and Hagan, 2002;Krien et al, 2002). NIMA-related kinases (NEKs) have also been identified in higher eukaryotes (Letwin et al, 1992;Schultz and Nigg, 1993;Lu and Hunter, 1995b;Chen et al, 1999;Tanaka and Nigg, 1999;Uto and Sagata, 2000;Kandli et al, 2000;Holland et al, 2002;Roig et al, 2002), some of which have been implicated in cell cycle progression.…”

A ‘marker switch’ approach for targeted mutagenesis of genes in Schizosaccharomyces pombe

“…The loss of function of the protein arising from the gene deletion is therefore masked as a substitute molecule can step in. The isolation of conditional lethal mutations in the non-essential fin1 + gene illustrates the need for caution in interpreting data from knock-out strains (Krien et al, 1998;Grallert and Hagan, 2002).…”

Spindle asymmetry: a compass for the cell

“…In many organisms, Cdk1 is found on spindles, spindle poles and astral MTs [49,72 -3], and the activity of Cdc2 -cyclin-B appears to be associated with centrosomes [74,75]. Cdc2 and other mitotic kinases also regulate the activities of MT-based motors and MAPs during spindle formation [76 -79].…”