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Thirty years of search and capture: The complex simplicity of mitotic spindle assembly

J Cell Biol. 2015 Dec 21;211(6):1103-11. doi: 10.1083/jcb.201510015. Epub 2015 Dec 14.

Heald R, Khodjakov A.

Abstract

Cell division is enacted by a microtubule-based, self-assembling macromolecular machine known as the mitotic spindle. In 1986, Kirschner and Mitchison proposed that by undergoing dynamic cycles of growth and disassembly, microtubules search for chromosomes. Capture of microtubules by the kinetochores progressively connects chromosomes to the bipolar spindle. 30 years later, "search and capture" remains the cornerstone of spindle assembly. However, a variety of facilitating mechanisms such as regulation of microtubule dynamics by diffusible gradients, spatially selective motor activities, and adaptive changes in chromosome architecture have been discovered. We discuss how these mechanisms ensure that the spindle assembles rapidly and with a minimal number of errors. © 2015 Heald and Khodjakov.

PMID 26668328

Box 1 Motor-dependent mechanisms establish bipolarity as Eg5 (kinesin-5) motors slide antiparallel microtubules apart with their minus ends leading and their plus ends directed toward the spindle equator.

Box 2 Minus end–directed motors such as dynein move microtubules poleward with their minus ends leading, thereby incorporating K-fibers into the spindle and focusing spindle poles.

Box 3 Kinetochore-associated dynein transports chromosomes along astral microtubules toward the spindle poles from the periphery.

Box 4 Plus end–directed chromokinesins (kinesin-4 and -10) eject chromosome arms outward.

Box 5 CENP-E (kinesin-7) transports unattached kinetochores toward the equator along spindle microtubules. MTOC, microtubule organizing centre.