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#spindle fibers

14 public questions tagged with this topic.

Cytoskeleton

During mitosis, kinetochore microtubules:

Kinetochore microtubule fibers K fibers dynamic behavior changes across mitotic stages governed by tension sensing checkpoint signaling and motor forces generating chromosome movement. During prometaphase microtubules nucleated at centrosomal poles probe cytoplasm via dynamic instability growth at plus end at several microns per minute capture kinetochore through NDC80 complex forming bundles of 20 to 40 microtubules stabilized by CLASP and formins. Until anaphase kinetochore microtubules continue polymerization at plus end while minus ends depolymerize at poleward flux mediated by kinesin-13 and katanin maintaining tension across sister chromatids bi oriented at metaphase plate. This tension stabilizes attachments via Aurora B spatial separation and silences spindle assembly checkpoint via removal of Mad2 BubR1. At anaphase onset after separase cleaves cohesin switch to coordinated depolymerization at both ends: plus end depolymerizes at kinetochore Pacman mechanism driven by kinesin-13 and Dam1 ring, minus end at pole, pulling chromosomes poleward segregation of genetic material without continuous growth throughout mitosis. Continuous growth not observed switch essential.

Ref: Cheeseman & Desai, Annu Rev Cell Dev Biol – Kinetochore microtubules polymerize until anaphase then depolymerize.

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Cell Division

What happens during prometaphase?

Prometaphase is transitional stage converting interphase nuclear architecture to mitotic spindle structure, initiated by rising cyclin B-CDK1 activity. CDK1 phosphorylates lamins A/C and B at serine residues within tail domain, causing depolymerization of filamentous lamina and fragmentation of nuclear envelope into vesicles merging with endoplasmic reticulum. Condensed chromosomes consisting of two sister chromatids embraced by cohesin are released into cytoplasm. Concurrently, kinetochores assembled at centromeres containing CENP-A nucleosomes fully mature, forming outer plate with KMN network composed of KNL1 scaffold, Mis12 complex, and Ndc80 complex that directly binds microtubule plus ends with high affinity. Motor proteins CENP-E kinesin and dynein mediate initial lateral capture of highly dynamic microtubules emanating from duplicated centrosomes, followed by conversion to stable end-on attachment capable of generating force via depolymerization-coupled pulling. Chromosome congression begins and spindle assembly checkpoint proteins Mad1, Mad2, Bub1, BubR1 accumulate at unattached kinetochores to delay anaphase. This circuitry is highly conserved across eukaryotes, integrating growth factor signals, DNA damage surveillance, and developmental cues, and its disruption frequently underlies oncogenesis, providing targets for checkpoint inhibitors and cancer therapeutics.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 17, Prometaphase Events.

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