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Cited by 13Microtubule and mitosis dynamicsProtein Kinase Regulation and GTPase SignalingCellular Mechanics and Interactions

The MgcRacGAP SxIP motif tethers Centralspindlin to microtubule plus ends in Xenopus laevis

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Breznau, Elaina B., Murt, Megan, Blasius, T. Lynne, Verhey, Kristen J., Miller, Ann L.·2017·Journal of Cell Science
DOI 10.1242/jcs.195891PMC PMC5450188
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Abstract

Centralspindlin, a complex of the kinesin-6-family member MKLP1 and MgcRacGAP (also known as Kif23 and Racgap1, respectively), is required for cytokinesis and cell–cell junctions. During anaphase, Centralspindlin accumulates at overlapping central spindle microtubules and directs contractile ring formation by recruiting the GEF Ect2 to the cell equator to activate RhoA. We found that MgcRacGAP localized to the plus ends of equatorial astral microtubules during cytokinesis in Xenopus laevis embryos. How MgcRacGAP is stabilized at microtubule plus ends is unknown. We identified an SxIP motif in X. laevis MgcRacGAP that is conserved with other proteins that bind to EB1 (also known as Mapre1), a microtubule plus-end tracking protein. Mutation of the SxIP motif in MgcRacGAP resulted in loss of MgcRacGAP tracking with EB3 (also known as Mapre3) on growing microtubule plus ends, abnormal astral microtubule organization, redistribution of MgcRacGAP from the contractile ring to the polar cell cortex, and mislocalization of RhoA and its downstream targets, which together contributed to severe cytokinesis defects. Furthermore, mutation of the MgcRacGAP SxIP motif perturbed adherens junctions. We propose that the MgcRacGAP SxIP motif is functionally important both for its role in regulating adherens junction structure during interphase and for regulating Rho GTPase activity during cytokinesis.

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  • RACGAP1 localizes to the central spindle in a microtubule-dependent manner during anaphase.

    “The protein localizes to the central spindle in a microtubule-dependent manner during anaphase”

    From Structural basis of microtubule-mediated signal transduction (2026) · cites this paper as [91]

    The Abstract and Discussion (pages not specified) state that Centralspindlin, which contains RACGAP1/MgcRacGAP, accumulates at the central spindle during anaphase. The paper describes microtubule-based delivery and tethering at microtubule plus ends, but the passages do not establish that its central-spindle localization is microtubule-dependent. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Breznau, E. B., Murt, M., Blasius, T. L., Verhey, K. J., & Miller, A. L.
Affiliations
University of Michigan (US)
ORCID
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2017-05-15
Volume
130
Issue
10
Pages
1809-1821
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
DOI
10.1242/jcs.195891
PMC
PMC5450188
OpenAlex
W2604736410
Cited by
13
References
0
Citations by year
2025: 1 · 2023: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 2
FWCI
1.31
Type
journal article
Language
en
Open access
Licence
www.biologists.com/user-licence-1-1/ (vor, 184 d)
Locations
  • Journal of Cell Science (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Institutes of Health (R00 GM089765, R01 GM112794, R01 GM070862, T32-GM007315, R01 GM52932)
  • National Science Foundation
  • Horace H. Rackham School of Graduate Studies, University of Michigan
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
MgcRacGAP, centralspindlin, microtubule plus ends, astral microtubules, EB1, EB3, contractile ring, cytokinesis, RhoA, Rho GTPases, MKLP1, ECT2, adherens junctions, Xenopus laevis embryos, cell cortex
MeSH terms
Actins, Amino Acid Sequence, Animals, Chlorocebus aethiops, Microtubules, Models, Biological, Mutation, Structure-Activity Relationship, Xenopus laevis, COS Cells, GTPase-Activating Proteins, rhoA GTP-Binding Protein, Amino Acid Motifs, Adherens Junctions, Xenopus Proteins, Cytokinesis, Time-Lapse Imaging

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