Prophase-Specific Perinuclear Actin Coordinates Centrosome Separation and Positioning to Ensure Accurate Chromosome Segregation

Prophase-Specific Perinuclear Actin Coordinates Centrosome Separation and Positioning to Ensure Accurate Chromosome Segregation

Centrosome separation in late G2/ early prophase requires precise spatial coordination that is determined by a balance of forces promoting and antagonizing separation. The major effector of centrosome separation is the kinesin Eg5. However, the identity and regulation of Eg5-antagonizing forces is l...

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Bibliographic Details
Published in:Cell reports (Cambridge) Vol. 31; no. 8; p. 107681
Main Authors: Stiff, Tom, Echegaray-Iturra, Fabio R., Pink, Harry J., Herbert, Alex, Reyes-Aldasoro, Constantino Carlos, Hochegger, Helfrid
Format: Journal Article
Language:English
Published: United States Elsevier Inc 26-05-2020
Cell Press
Elsevier
Subjects:
Actins - metabolism
Centrosome - metabolism
centrosome positioning
centrosome separation
centrosome tracking
Chromosome Segregation - genetics
Eg5
FHOD1
G2/M transition
Humans
LINC complex
mitotic entry
perinuclear actin, microtubules
Prophase - genetics
Eg5
centrosome tracking
centrosome separation
FHOD1
G2/M transition
perinuclear actin, microtubules
LINC complex
centrosome positioning
mitotic entry
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Summary:Centrosome separation in late G2/ early prophase requires precise spatial coordination that is determined by a balance of forces promoting and antagonizing separation. The major effector of centrosome separation is the kinesin Eg5. However, the identity and regulation of Eg5-antagonizing forces is less well characterized. By manipulating candidate components, we find that centrosome separation is reversible and that separated centrosomes congress toward a central position underneath the flat nucleus. This positioning mechanism requires microtubule polymerization, as well as actin polymerization. We identify perinuclear actin structures that form in late G2/early prophase and interact with microtubules emanating from the centrosomes. Disrupting these structures by breaking the interactions of the linker of nucleoskeleton and cytoskeleton (LINC) complex with perinuclear actin filaments abrogates this centrosome positioning mechanism and causes an increase in subsequent chromosome segregation errors. Our results demonstrate how geometrical cues from the cell nucleus coordinate the orientation of the emanating spindle poles before nuclear envelope breakdown. [Display omitted] •Dynein and the actin/MT network coordinate centrosome positioning and separation•The MT/actin network antagonizes Eg5-dependent separation•LINC-complex-dependent perinuclear actin is critical for this mechanism•Disrupting the LINC/actin interaction results in centrosome mis-positioning Stiff et al. describe how prophase-specific perinuclear actin in connection with polymerizing microtubules regulates the positioning of centrosome separation before nuclear envelope breakdown. This depends on the interaction of the LINC complex with actin. Breaking this link results in centrosome mispositioning and an increase in sister chromatid segregation errors.
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These authors contributed equally
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2020.107681