High impact information on BIK1

• The MT plus end-binding proteins Kar3p, a class 14 COOH-terminal kinesin, and Bik1p, the CLIP-170 orthologue, localize to plus ends in the shmoo tip and initiate MT interactions and depolymerization after cell wall breakdown [1].
• The ploidy-specific requirement for BIK1 enabled us to characterize BIK1 without eliminating nonhomologous genes, providing a new approach to circumventing the overlapping function that is a common feature of the cytoskeleton [2].
• Polyploids require Bik1 for kinetochore-microtubule attachment [2].
• The role of Bik1 in kinetochore separation appears to be independent of the role of Bik1 in regulating MT dynamics [2].
• Strikingly, Bik1 is not required for viability in haploid cells, but becomes essential in polyploids [2].

Biological context of BIK1

• The region of Saccharomyces cerevisiae chromosome III located between the 5' end of the HIS4 gene and the 3' end of the adjacent BIK1 gene has a very high level of meiotic recombination [3].
• Based on these results, we propose that BIK1 is required stoichiometrically for the formation or stabilization of microtubules during mitosis and for spindle pole body fusion during conjugation [4].
• This phenotype is partially rescued by S. cerevisiae BIK1 [5].
• The CLIP-170 homologue Bik1p promotes the phosphorylation and asymmetric localization of Kar9p [6].
• In polyploid cells, Bik1 is required before anaphase to maintain kinetochore separation and therefore contributes to the force that opposes the elastic recoil of attached sister chromatids [2].

Anatomical context of BIK1

• Cells overexpressing BIK1 initially have abnormally short or nonexistent spindle microtubules and long cytoplasmic microtubules [4].
• Spindle formation often occurs strictly within the mother cell, probably accounting for the many multinucleate and anucleate bik1 cells [4].
• Nuclear fusion is blocked in bik1 x bik1 zygotes, which have truncated cytoplasmic microtubules [4].

Associations of BIK1 with chemical compounds

• A phosphomimetic mutation at serine 496 bypasses the requirement of BIK1 and CLB5 in generating Kar9p asymmetry [7].

Physical interactions of BIK1

• Here, we show that the CLIP-170 homologue Bik1p binds directly to Kar9p [6].
• Bik1 forms a complex with the kinesin Kip2 [8].

Enzymatic interactions of BIK1

• Kar9p is hypophosphorylated in bik1delta mutants, and Bik1p binds to both phosphorylated and unphosphorylated isoforms of Kar9p [6].

Regulatory relationships of BIK1

• Together, these data suggest that Bik1p promotes the phosphorylation of Kar9p on serine 496, which affects its asymmetric localization to one SPB and associated cytoplasmic MTs [6].

Other interactions of BIK1

• Strains lacking both ASE1 and BIK1, which encodes an S. cerevisiae microtubule-associated protein, are inviable [9].
• Furthermore, the two-hybrid interaction between full-length KAR9 and the cyclin CLB5 requires BIK1 [6].
• In support of this possibility, we find that Fus3 is activated to a greater extent in a "wimp" strain with defective protein kinase A. Finally, BIM1 and BIK1 have been identified as CEN suppressors of far5, suggesting that the microtubule apparatus may regulate the ability of the pheromone response pathway to promote G1 arrest [10].
• Synthetic lethality observed in double mutant strains containing a mutation in the BIK1 gene and in the gene for alpha- or beta-tubulin is consistent with a physical interaction between BIK1 and tubulin [4].
• Thus, Stu2, Bik1, and Bim1 interact physically but do not appear to be arranged in a single unique complex [11].

Analytical, diagnostic and therapeutic context of BIK1

• In addition to presenting functional comparisons between Bik1p and CLIP-170, we provide sequence analyses that reveal previously unrecognized similarities between Bik1p and its animal counterparts [12].

References