Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes

Melpomeni Platani; Laura Trinkle-Mulcahy; Michael Porter; A. Arockia Jeyaprakash; William C. Earnshaw

doi:10.1083/jcb.201410001

Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes

Melpomeni Platani (Lead / Corresponding author)
, Laura Trinkle-Mulcahy
, Michael Porter
, A. Arockia Jeyaprakash
, William C. Earnshaw

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

Abstract

Coordination of cell growth and proliferation in response to nutrient supply is mediated by mammalian target of rapamycin (mTOR) signaling. In this study, we report that Mio, a highly conserved member of the SEACAT/GATOR2 complex necessary for the activation of mTORC1 kinase, plays a critical role in mitotic spindle formation and subsequent chromosome segregation by regulating the proper concentration of active key mitotic kinases Plk1 and Aurora A at centrosomes and spindle poles. Mio-depleted cells showed reduced activation of Plk1 and Aurora A kinase at spindle poles and an impaired localization of MCAK and HURP, two key regulators of mitotic spindle formation and known substrates of Aurora A kinase, resulting in spindle assembly and cytokinesis defects. Our results indicate that a major function of Mio in mitosis is to regulate the activation/deactivation of Plk1 and Aurora A, possibly by linking them to mTOR signaling in a pathway to promote faithful mitotic progression.

Original language	English
Pages (from-to)	45-62
Number of pages	18
Journal	Journal of Cell Biology
Volume	210
Issue number	1
DOIs	https://doi.org/10.1083/jcb.201410001
Publication status	Published - 6 Jul 2015

Keywords

Amino acid sequence
Aurora kinase A
Cell cycle proteins
Centrosome
Enzyme activation
Gene knockdown techniques
HeLa cells
Humans
Kinesin
Mitosis
Molecular sequence data
Neoplasm proteins
Nuclear pore complex proteins
Protein structure, Tertiary
Protein transport
Protein-serine-threonine kinases
Proto-oncogene proteins
Spindle apparatus
TOR serine-threonine kinases

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10.1083/jcb.201410001Licence: CC BY-NC-SA

The Open Microscopy Environment: Image Informatics for Biological Sciences (Joint with Imperial College, Oxford University, Institut Pasteur, Carnegie-Mellon University, University of Wisconsin, Harvard Medical School & University of Edinburgh)
Swedlow, J. (Investigator)
1/10/11 → 30/09/16
Project: Research

Quantitative Characterisation of Morphological and Phenotypic Changes During Microbial Cell Differentiation and Multicellular Behaviour
Porter, M. (Author), Stanley-Wall, N. (Supervisor) & Swedlow, J. (Supervisor), 2020
Student thesis: Doctoral Thesis › Doctor of Philosophy

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title = "Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes",

abstract = "Coordination of cell growth and proliferation in response to nutrient supply is mediated by mammalian target of rapamycin (mTOR) signaling. In this study, we report that Mio, a highly conserved member of the SEACAT/GATOR2 complex necessary for the activation of mTORC1 kinase, plays a critical role in mitotic spindle formation and subsequent chromosome segregation by regulating the proper concentration of active key mitotic kinases Plk1 and Aurora A at centrosomes and spindle poles. Mio-depleted cells showed reduced activation of Plk1 and Aurora A kinase at spindle poles and an impaired localization of MCAK and HURP, two key regulators of mitotic spindle formation and known substrates of Aurora A kinase, resulting in spindle assembly and cytokinesis defects. Our results indicate that a major function of Mio in mitosis is to regulate the activation/deactivation of Plk1 and Aurora A, possibly by linking them to mTOR signaling in a pathway to promote faithful mitotic progression.",

keywords = "Amino acid sequence, Aurora kinase A, Cell cycle proteins, Centrosome, Enzyme activation, Gene knockdown techniques, HeLa cells, Humans, Kinesin, Mitosis, Molecular sequence data, Neoplasm proteins, Nuclear pore complex proteins, Protein structure, Tertiary, Protein transport, Protein-serine-threonine kinases, Proto-oncogene proteins, Spindle apparatus, TOR serine-threonine kinases",

author = "Melpomeni Platani and Laura Trinkle-Mulcahy and Michael Porter and Jeyaprakash, \{A. Arockia\} and Earnshaw, \{William C.\}",

note = "{\textcopyright} 2015 by The Rockefeller University Press.",

year = "2015",

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doi = "10.1083/jcb.201410001",

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T1 - Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes

AU - Platani, Melpomeni

AU - Trinkle-Mulcahy, Laura

AU - Porter, Michael

AU - Jeyaprakash, A. Arockia

AU - Earnshaw, William C.

PY - 2015/7/6

Y1 - 2015/7/6

N2 - Coordination of cell growth and proliferation in response to nutrient supply is mediated by mammalian target of rapamycin (mTOR) signaling. In this study, we report that Mio, a highly conserved member of the SEACAT/GATOR2 complex necessary for the activation of mTORC1 kinase, plays a critical role in mitotic spindle formation and subsequent chromosome segregation by regulating the proper concentration of active key mitotic kinases Plk1 and Aurora A at centrosomes and spindle poles. Mio-depleted cells showed reduced activation of Plk1 and Aurora A kinase at spindle poles and an impaired localization of MCAK and HURP, two key regulators of mitotic spindle formation and known substrates of Aurora A kinase, resulting in spindle assembly and cytokinesis defects. Our results indicate that a major function of Mio in mitosis is to regulate the activation/deactivation of Plk1 and Aurora A, possibly by linking them to mTOR signaling in a pathway to promote faithful mitotic progression.

AB - Coordination of cell growth and proliferation in response to nutrient supply is mediated by mammalian target of rapamycin (mTOR) signaling. In this study, we report that Mio, a highly conserved member of the SEACAT/GATOR2 complex necessary for the activation of mTORC1 kinase, plays a critical role in mitotic spindle formation and subsequent chromosome segregation by regulating the proper concentration of active key mitotic kinases Plk1 and Aurora A at centrosomes and spindle poles. Mio-depleted cells showed reduced activation of Plk1 and Aurora A kinase at spindle poles and an impaired localization of MCAK and HURP, two key regulators of mitotic spindle formation and known substrates of Aurora A kinase, resulting in spindle assembly and cytokinesis defects. Our results indicate that a major function of Mio in mitosis is to regulate the activation/deactivation of Plk1 and Aurora A, possibly by linking them to mTOR signaling in a pathway to promote faithful mitotic progression.

KW - Amino acid sequence

KW - Aurora kinase A

KW - Cell cycle proteins

KW - Centrosome

KW - Enzyme activation

KW - Gene knockdown techniques

KW - HeLa cells

KW - Humans

KW - Kinesin

KW - Mitosis

KW - Molecular sequence data

KW - Neoplasm proteins

KW - Nuclear pore complex proteins

KW - Protein structure, Tertiary

KW - Protein transport

KW - Protein-serine-threonine kinases

KW - Proto-oncogene proteins

KW - Spindle apparatus

KW - TOR serine-threonine kinases

U2 - 10.1083/jcb.201410001

DO - 10.1083/jcb.201410001

M3 - Article

C2 - 26124292

SN - 0021-9525

VL - 210

SP - 45

EP - 62

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 1

ER -

Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes

Abstract

Keywords

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Projects

The Open Microscopy Environment: Image Informatics for Biological Sciences (Joint with Imperial College, Oxford University, Institut Pasteur, Carnegie-Mellon University, University of Wisconsin, Harvard Medical School & University of Edinburgh)

Student theses

Quantitative Characterisation of Morphological and Phenotypic Changes During Microbial Cell Differentiation and Multicellular Behaviour

Cite this