Non-centrosomal microtubules at kinetochores promote rapid chromosome biorientation during mitosis in human cells

Abstract

Highlights d Amphitelic attachments form synchronously at a specific stage of spindle elongation d Amphitelic attachments form within a spatial domain defined by microtubule bundles d Bundles of antiparallel microtubules facilitate chromosome biorientation d CenpE and dynein at kinetochore affect the efficiency and rapidity of biorientation

Augmin-dependent microtubule self-organization drives kinetochore fiber maturation in mammals

“…In addition, our laser-mediated partial k-fiber injury/repair assay directly demonstrates a role for augmin in MT amplification from pre-existing kMTs. Together with our measurements of kMT turnover and direct observation of MT growth events within individual k-fibers, our data provide definitive evidence for a role of augmin-mediated MT amplification in k-fiber maturation, while reconciling this mechanism with growing evidence for centrosome-independent self-organization of kMTs during spindle assembly in animal cells, including human ( Conway et al., 2021 ; Maiato et al., 2004 ; Renda et al., 2022 ; Sikirzhytski et al., 2018 ).…”

“…In these cases, short MTs nucleated in the vicinity of and subsequently oriented and captured by KTs ( Maiato et al., 2004 ; Sikirzhytski et al., 2018 ) might work as amplification platforms for augmin-mediated self-organization of k-fibers, while still ensuring the directional bias of MT growth toward the KT, independently of centrosomes. When centrosomes are present, augmin-dependent MT amplification of short kMT stubs might promote efficient chromosome biorientation through capture of pre-formed k-fibers by astral MTs ( Elting et al., 2014 ; Khodjakov et al., 2003 ; Maiato et al., 2004 ; Sikirzhytski et al., 2014 ) or by lateral interactions with an interpolar spindle scaffold that forms soon after nuclear envelope breakdown ( Nunes et al., 2020 ; Renda et al., 2022 ) and will give rise to bridging fibers ( Kajtez et al., 2016 ) graphical abstract .…”

Polar Chromosomes—Challenges of a Risky Path

“…Central chromosomes that are not located within the nascent spindle are transported directly to the spindle equator, where they become rapidly bioriented (Figure 1A, route 2) or first undergo a poleward-directed movement on the emerging spindle before initiating congression towards the equatorial plane [20][21][22] (Figure 1A, route 3). These movements depend on the kinetochore motors to a different extent [23]. Lastly, peripheral polar chromosomes, comprising 10-20% of all chromosomes, first move poleward before initiating congression towards the equatorial plane (Figure 1A, route 4), which strongly depends on kinetochore motors [7,18].…”

“…This is probably the case for most polar chromosomes located behind the spindle pole [18], where astral MTs display unidirectional polarity with plus ends protruding toward the cell cortex and minus ends embedded in the centrosome [2]. However, in the central region away from the spindle, chromosomes often show surprisingly fast orthogonal movements of kinetochores by which they come close to the spindle equator [23], whose mechanism is not completely known.…”

Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly

“…Overlap or interpolar bundles consist of antiparallel microtubules that extend from the opposite spindle halves 6 . Spindle assembly has been extensively studied with focus on kinetochore dynamics and the formation of kinetochore fibers [7][8][9][10][11][12] , whereas the mechanism of overlap bundle formation remains poorly understood.…”