Chromosome segregation during cell division depends on the highly ordered bipolar microtubule structure known as the mitotic spindle. Organization of microtubules into this highly ordered structure relies on both motor and nonmotor proteins. Nonmotor spindle proteins fulfill diverse roles including nucleation and organization of microtubules, regulation of spindle shape and size, regulation of motor activity and microtubule dynamics, as well as control of chromosome segregation and cell-cycle progression. Many nonmotor spindle proteins display distinct localization patterns in mitosis, and several contribute to more than one functional activity within the spindle. Given this complexity, it is not surprising that nonmotor proteins frequently show altered expression patterns in cancer or mutations in human diseases.
| Protein name | Species | Localization | Function in Spindle Assembly | |
|---|---|---|---|---|
| Microtubule Nucleation/Stabilization | DGT/augmin complex | Human, fly | Spindle microtubules | Boosts microtubule number by regulating γ-tubulin |
| NuSAP | Human, mouse, frog | Central spindle | Nucleation, stabilization, and bundling of microtubules near chromosomes | |
| *RHAMM/HMMR | Human, mouse, frog (XRHAMM) | Centrosomes, spindle poles, spindle midbody | Nucleates and stabilizes microtubules at spindle poles; influences cyclin B1 activity | |
| *TACC 1-3 | Human, mouse, fly (D-TACC), worm (TAC-1), frog (Maskin), Sp (Alp7) | Centrosomes, spindle poles | Promotes microtubule nucleation and stabilization at spindle poles | |
| *TOGp | Human, mouse, fly (Minispindles/Msps), worm (ZYG-9), frog (XMAP215/Dis1), Sc (Stu2), Sp (Dis1/Alp14) | Centrosomes, spindle poles | Promotes centrosome and spindle pole stability; promotes plus-end microtubule dynamics | |
| Microtubule Crosslinking/Stabilization | Astrin | Human, mouse (Spag5) | Spindle poles, kinetochores | Crosslinks and stabilizes microtubules at spindle poles and kinetochores; stabilizes cohesin |
| *HURP/DLG7 | Human, mouse, fly, worm, frog, Sc | Kinetochore fibers, most intense near kinetochores | Stabilizes kinetochore fiber; influences chromosome alignment | |
| *NuMA | Human, mouse, fly (Mud/Asp1), frog | Spindle poles | Formation/maintenance of spindle poles; inhibits APC/C at spindle poles | |
| *Prc1 | Human, mouse, fly (Fascetto/Feo), worm (SPD-1), frog, Sc (Ase1), Sp (Ase1) | Central spindle, spindle midbody | Stabilizes anaphase spindle elongation by crosslinking antiparallel spindle midzone microtubules | |
| Tektin 2 | Human, mouse, fly, worm, frog, | Centrosomes, midbody | Bundles microtubules of the midbody to allow cytokinesis | |
| *TPX2 | Human, mouse, fly (Asp1), worm (TPXL-1), frog | Spindle poles, spindle midbody | Promotes microtubule nucleation and centrosome integrity; activates Aurora A; crosslinks microtubules at spindle poles | |
| Microtubule Severance/Destabilization | *DDA3 | Human, mouse | Spindle microtubules, midbody | Bundles microtubules; regulates the spindle pole localized microtubule depolymerase Kif2a |
| Fidgetin | Human, mouse (Fignl1), fly (Fignl1), worm (FIGL-1), frog (Fignl1) | Centrosomes | Catalyzes turnover of γ-tubulin; contributes to microtubule depolymerization and chromosome movement | |
| Katanin | Human, mouse (Katnb1), fly, worm (MEI), frog, Sc | Centrosomes, chromatin | Promotes microtubule plus-end depolymerization; contributes to pole-ward chromosome movement | |
| *Op18/Stathmin | Human, mouse (Stathmin), fly (Stathmin), frog (Stathmin) | Centrosomes, spindle poles | Regulates microtubule dynamics by promoting depolymerization and sequestering of tubulin dimers | |
| *Spastin | Human, mouse, fly (D-Spastin), worm, frog | Spindle poles, spindle midbody | Catalyzes turnover of γ-tubulin; contributes to microtubule depolymerization and chromosome movement | |
| + Tip Trackers | *APC | Human, mouse, fly, worm (APR-1), frog, Sc (Kar9) | Growing microtubule plus ends | Stabilizes microtubule plus ends; influences chromosome alignment |
| CLASP1, 2 | Human, mouse, fly (MAST/Orbit), worm (CLS-2) Sp (Peg1) | Growing microtubule plus ends | Stabilizes plus-end microtubule dynamics; influences spindle formation and chromosome alignment | |
| CLIP170 | Human, mouse, fly, frog, Sc (Bik1), Sp (Tip1) | Growing microtubule plus ends | Regulates plus-end microtubule dynamics by promoting rescue of depolymerization | |
| *Lis1 | Human, mouse, fly, worm, frog, Sc (Pac1) | Growing microtubule plus ends | Recruits dynein to microtubule plus ends | |
| *MAPRE1/Eb1 | Human, mouse, fly, worm, frog, Sc (Bim1), Sp (Mal3) | Growing microtubule plus ends | Regulates growth of microtubule plus ends by suppressing depolymerization; influences chromosome alignment | |
| Chromosomal Passenger Complex | *Aurora B | Human, mouse (AIM-1), fly (Lal), worm (AIR-2) frog, Sc (Ipl1), Sp (ARK1) | Inner centromeres in metaphase, central spindle/midbody in anaphase | Regulates spindle structure, kinetochore-microtubule attachment, and error correction; mitotic progression, cytokinesis |
| *Borealin | Human, mouse, fly (Borr), worm (CSC-1), frog (Dasra) | Inner centromeres in metaphase, central spindle/midbody in anaphase | Controls the localization and activity of Aurora B | |
| INCENP | Human, mouse, fly, worm (ICP-1), frog, Sc (Sli15), Sp (Plc1) | Inner centromeres in metaphase, central spindle/midbody in anaphase | Controls the localization and activity of Aurora B | |
| *Survivin | Human, mouse, fly (Deterin), frog, worm (BIR-1), Sc (Bir1), Sp (Bir1/Cut17) | Inner centromeres in metaphase, central spindle/midbody in anaphase | Controls the localization and activity of Aurora B; protects against apoptosis | |
| TD60 | Human, mouse, fly, frog | Inner centromeres in metaphase, central spindle/midbody in anaphase | Activates the kinase activity of Aurora B | |
| Others | CHICA | Human | Spindle microtubules | Polar ejection in cooperation with the chromokinesin Kid |
| Chromator | Fly | Fusiform spindle shape around spindle microtubules | Forms a microtubule-independent fusiform spindle; influences bipolar spindle formation; putative spindle matrix protein | |
| *Dynactin | Human, mouse, fly, worm, frog, Sc, Sp | Spindle poles, kinetochores, spindle midbody | Coactivator of dynein, required for dynein functions including spindle pole focusing and chromosome movement | |
| *Lamin B | Human, mouse, fly, worm, frog | Spindle microtubules | Promotes microtubule assembly and organization; putative spindle matrix protein | |
| Megator | Fly | Fusiform spindle shape around spindle microtubules | Forms complex with Skeletor/Chromator; forms microtubule-independent fusiform spindle; putative spindle matrix protein | |
| Skeletor | Fly | Fusiform spindle shape around spindle microtubules | Forms a microtubule-independent fusiform spindle; putative spindle matrix protein | |
| *Tankyrase | Human, mouse, fly, worm (PME-5), frog | Spindle poles | Contributes to spindle pole focusing; putative spindle matrix protein | |
| Vik1 | Sc | Spindle pole body | Influences microtubule stability by regulation of the kinesin Kar3 |
*
overexpression or mutation linked to human cancer or other diseases
Sp, Schizosaccharomyces pombe
Sc, Saccharomyces cerevisiae
Acknowledgments
D.A.C. is supported by the National Institutes of Health (GM51542). A.L.M. is supported by a John H. Copenhaver, Jr. and William H. Thomas, M.D. 1952 Junior Fellowship.
Abbreviations
- APC
Adenomatosis Polyposis Coli
- Astrin
Aster-associated protein
- CLASP1/2
Cytoplasmic Linker-Associated Protein
- CLIP170
CAP-GLY Domain-Containing Linker Protein
- DDA3
Differential Display Activated by p53
- DGT
Dim γ-tubulin
- HURP/DLG7
Hepatoma Upregulated Protein
- INCENP
INner CENtromere Protein
- Lis1
Lissencephaly 1
- MAPRE1/Eb1
Microtubule-Associated Protein, RP/EB family, member 1
- NuMA
Nuclear Mitotic Apparatus
- NuSAP
Nucleolar Spindle-Associated Protein
- Op18/Stathmin
Oncoprotein 18
- Prc1
Protein Regulator of Cytokinesis
- RHAMM/HMMR
Receptor of Hyaluronan-Mediated Motility
- TACC 1-3
Transforming Acidic Coiled-Coil
- Tankyrase
TRF1-interacting Ankyrin-Related ADP-ribose
- TD60
Telophase Disk 60kDa
- TOGp
Tumor Overexpressed Gene
- TPX2
Targeting Protein for Xklp2
- Vik1
Vegetative Interaction with Kar3
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