Control of Mitotic Spindle Length

Abstract

The mitotic spindle accurately segregates genetic instructions by moving chromosomes to spindle poles (anaphase A) and separating the poles (anaphase B) so that, in general, the chromosomes and poles are positioned near the centers of the nascent daughter cell products of each cell division. Because the size of different types of dividing cells, and thus the spacing of their daughter cell centers, can vary significantly, the length of the metaphase or postanaphase B spindle often scales with cell size. However, significant exceptions to this scaling rule occur, revealing the existence of cell size–independent, spindle-associated mechanisms of spindle length control. The control of spindle length reflects the action of mitotic force-generating mechanisms, and its study may illuminate general principles by which cells regulate the size of internal structures. Here we review molecules and mechanisms that control spindle length, how these mechanisms are deployed in different systems, and some quantitative models that describe the control of spindle length.

APC/C is an essential regulator of centrosome clustering

“…Moreover, it does not take into account that spindle length and stability is dependent on both inter-polar microtubule interactions and microtubulechromosome interactions [27][28][29] . Based on our data we propose the following model: in cancer cells with CA, a balance of inward and outward forces exerted on spindle poles via K-fibres and cross-linked anti-parallel microtubules [28][29][30][31][32] is essential to allow movement of spindle poles relative to each other. Microtubules growing from the microtubule organizing centres can pivot toward and capture kinetochores forming the K-fibres in a stochastic model termed 'search-and-capture'.…”

“…Microtubules growing from the microtubule organizing centres can pivot toward and capture kinetochores forming the K-fibres in a stochastic model termed 'search-and-capture'. K-fibres, together with cross-linked antiparallel microtubules and/or microtubules attached to chromosome arms that exert outward pull forces on opposing poles maintain spindle length and stability [27][28][29] . Thus, flexibility of the spindle microtubules and precise titration of opposing spindle pole forces in mitosis are necessary for proper spindle function.…”

Endogenous localizome identifies 43 mitotic kinesins in a plant cell

“…In humans, ∼20 of 45 kinesins have been identified as mitotic kinesins by RNAi and localization analyses using several cell types (2,5,6). Most kinesins exert forces toward MTs or chromosomes; therefore, the identification of kinesins localized to the mitotic apparatus has significantly contributed to the understanding of the mechanisms underlying mitosis, such as spindle bipolarity establishment, spindle elongation, or chromosome movement (7)(8)(9).…”

The Essentiality of the Fungus-Specific Dam1 Complex Is Correlated with a One-Kinetochore-One-Microtubule Interaction Present throughout the Cell Cycle, Independent of the Nature of a Centromere

“…The Dam1 complex (described below) in S. cerevisiae has been shown to be a coupler that transduces MT depolymerization activity into poleward pulling forces. Nonkinetochore/interpolar MTs (IPMTs), which interdigitate at the spindle midzone with the help of plus-end MT binding proteins (4, 32), elongate to generate outward pushing forces to further separate sister chromatids during anaphase B. Cytoplasmic/ astral MTs that protrude toward the cytoplasm (41) regulate spindle length and alignment (20). The interaction of astral MTs with the cell cortex generates backward force that acts on spindle poles and keeps them at a specific distance apart from each other (7,33,39,41,46).…”