Differential Regulation of the Kar3p Kinesin-related Protein by Two Associated Proteins, Cik1p and Vik1p

Abstract

The mechanisms by which kinesin-related proteins interact with other proteins to carry out specific cellular processes is poorly understood. The kinesin-related protein, Kar3p, has been implicated in many microtubule functions in yeast. Some of these functions require interaction with the Cik1 protein (Page, B.D., L.L. Satterwhite, M.D. Rose, and M. Snyder. 1994. J. Cell Biol. 124:507–519). We have identified a Saccharomyces cerevisiae gene, named VIK1, encoding a protein with sequence and structural similarity to Cik1p. The Vik1 protein is detected in vegetatively growing cells but not in mating pheromone-treated cells. Vik1p physically associates with Kar3p in a complex separate from that of the Kar3p-Cik1p complex. Vik1p localizes to the spindle-pole body region in a Kar3p-dependent manner. Reciprocally, concentration of Kar3p at the spindle poles during vegetative growth requires the presence of Vik1p, but not Cik1p. Phenotypic analysis suggests that Cik1p and Vik1p are involved in different Kar3p functions. Disruption of VIK1 causes increased resistance to the microtubule depolymerizing drug benomyl and partially suppresses growth defects of cik1Δ mutants. The vik1Δ and kar3Δ mutations, but not cik1Δ, partially suppresses the temperature-sensitive growth defect of strains lacking the function of two other yeast kinesin-related proteins, Cin8p and Kip1p. Our results indicate that Kar3p forms functionally distinct complexes with Cik1p and Vik1p to participate in different microtubule-mediated events within the same cell.

pkl1+andklp2+: Two Kinesins of the Kar3 Subfamily in Fission Yeast Perform Different Functions in Both Mitosis and Meiosis

“…In contrast, pkl1⌬ increases the sensitivity of fission yeast to a MT poison, whereas cik1⌬ has the same effect on budding yeast (Figure 2; Page et al, 1994). Moreover, klp2⌬ in S. pombe and cik1⌬ in S. cerevisiae provide resistance to MT poisons (Figure 2; Manning et al, 1999). In addition, the deletion of VIK1 partially rescues the cik1⌬ phenotype, similar to the effect seen when Klp2 is deleted in a pkl1⌬,cut11-1 background in S. pombe.…”

“…Thus, although there is little evidence to support this model, we cannot conclude on current evidence that Kar3p is not kinetochore-associated in budding yeast. Kar3p in budding yeast binds with two distinct companion polypeptides, Cik1p (Page et al, 1994) and Vik1p (Manning et al, 1999). These associated proteins bind with Kar3p and help to localize it to different places (Vik1p to the poles and Cik1p to the spindle and to "nuclear patches"), and they seem to induce it to perform different functions.…”

Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process

“…1b). This may be related to the Cik1-independent Kar3 function, which is shared with Vik1 and Cin8, at the mitotic spindle poles 36 DSB survival (Fig. 1b).…”

“…6d) 36,49,50 . kar3-1 and kar3-898 are two Kar3 motor domain mutants that fail to hydrolyse ATP either in general or upon microtubule binding, respectively 49 .…”

When yeast cells meet, karyogamy!

“…38 Two proteins with independent MT binding activity, Cik1 and its homolog Vik1, form distinct heterodimeric complexes with Kar3, with each distinct functions. [39][40][41] Of these, the Kar3/ Cik1 heterodimer is required for mating, where a mating-specific Kar3/Cik1 from the outer plaque of the SPB to the half-bridge.…”