cut7 (kinesin-5) — S. pombe — review notes
UniProt P24339 / SPAC25G10.07c. Sole kinesin-5 (BimC/Eg5 family) in fission yeast. Essential for mitosis.
Identity / family
- Kinesin-like protein; N-terminal kinesin motor domain (UniProt FT DOMAIN 72..421), ATP-binding P-loop (BINDING 159..166). BimC subfamily (UniProt SIMILARITY: "Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. BimC subfamily.").
- 1085 aa; coiled-coil regions (436..604, 715..740, 897..955) consistent with homotetramer formation. CDC2 phosphosite Thr1011 (by similarity).
Discovery / core phenotype
- PMID:2145514 and "Mutations at cut7 block spindle formation" (UniProt). cut7 resembles A. nidulans bimC; mutants form two unconnected half spindles, chromosome separation fails.
- PMID:1538784 — localization to SPB, mitotic+meiotic spindle, anaphase B midzone.
Motor activity / direction
- PMID:27834216; bidirectional motor — "the key determinant of stepping direction is the degree of motor crowding on the microtubule lattice, with greater crowding converting the motor from minus end-directed to plus end-directed stepping." Plus- AND minus-end-directed motor activity directly demonstrated. "the Cut7 N terminus increases Cut7 occupancy by binding directly to microtubules" (microtubule binding).
- PMID:30659798; "Cut7, the sole kinesin-5 in fission yeast, was among the first mitotic kinesins to be identified and is essential for spindle pole body separation." Motor domain (residues 67–432) ATPase measured: "Cut7MD has a very slow ATPase activity in vitro" with Vmax ~1.14 ATP/s; "the C-terminal neck linker ... docking along the length of the motor domain and directed toward the MT plus end" = plus-end directed; binds MT via helix-α4. Forms "dumbbell shaped antiparallel tetramers that support spindle MT cross linking and sliding." Cut7 is STLC-resistant (not inhibited by human kinesin-5 inhibitor).
Spindle force balance / antagonism
- PMID:24239120; "Upon inactivation of cut7p at the non-permissive 35°C, the metaphase spindle immediately shortened until the spindle became a focused monopolar structure ... cut7p being the major contributor to the outward pushing force." cut7 phase-one mitotic spindle formation IMP.
- PMID:28513584; cut7Δpkl1Δ rescues bipolarity (force balance restored); "spindle elongation velocity during anaphase B was reduced in cut7Δpkl1Δ cells (30% reduction ...), suggesting that Cut7 participates in anaphase spindle elongation in addition to its established function in spindle bipolarity." — supports phase-three elongation role.
- PMID:18418055 cut7-22(ts) bipolarity defects rescued by stabilizing MTs / deleting kinesin-14 pkl1; "the conditional allele cut7-22(ts), encoding fission yeast mitotic Kinesin-5, essential for bipolarity." Genetic interaction with MTOC/pkl1 — basis of IGI mitotic spindle midzone assembly.
Kinetochore / chromosome congression (Mad1)
- PMID:26258632; "Mad1 recruits Cut7 to kinetochores of misaligned chromosomes and promotes chromosome gliding towards the spindle equator." — basis of kinetochore localization (IDA), Mad1 (P87169 / SPBC3D6.04c) interaction (IPI), and microtubule plus-end directed mitotic chromosome migration (IGI). Note: this is a context-specific (misaligned chromosome) role, not the core bipolar-spindle function.
Meiosis
- PMID:32327557; Cut7-GFP "localized to the spindle and spindle poles from spindle assembly to spindle disassembly during both mitosis and MI." cut7Δpkl1Δ zygotes fail MI bipolar spindle (meiosis-specific requirement; kinesin-14 Klp2 and MT dynamics also antagonize Cut7 in MI). Supports meiotic spindle / meiotic spindle pole localization and meiotic spindle assembly. Polar microtubule IDA also from this paper (PMID:32327557).
Localization (high-throughput)
- PMID:16823372 genome-wide YFP localization (ORFeome). Supports HDA nucleus, microtubule cytoskeleton, mitotic SPB localizations (consistent with directed-evidence localizations).
Interaction partners (IPI, PMID:30659798 listed PomBase IDs)
- SPBC16A3.15c, SPBC26H8.07c, SPBC800.05c — partners reported with cut7; these are listed as protein-binding IPIs. (Use of bare "protein binding" is uninformative per guidelines; better captured by MF microtubule motor activity / specific complex terms, but the experimental interaction itself is sound.)
Summary of core functions
- MF: plus-end-directed (and context-dependent minus-end-directed) microtubule motor activity; ATP binding / ATP hydrolysis; microtubule binding.
- BP: mitotic bipolar spindle assembly / initial SPB separation (phase one); spindle elongation (phases two/three); meiotic spindle assembly. Outward pushing force; antagonizes kinesin-14 Pkl1/Klp2.
- CC: spindle pole body (mitotic + meiotic), spindle microtubule / polar microtubule, spindle midzone, kinetochore (Mad1-dependent, context-specific).