Evidence map›Paper›PMID 27562601›Full record

ArticleEMBO reports2016

ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules.

Marta Gai, Federico T Bianchi, Cristiana Vagnoni, Fiammetta Vernì, Silvia Bonaccorsi, Selina Pasquero, Gaia E Berto, Francesco Sgrò, Alessandra Ma Chiotto, Laura Annaratone and 6 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in EMBO reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 83 citations in OpenAlex.

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  18. ASPM promotes ATR-CHK1 activation and stabilizes stalled replication forks in response to replication stress.Proceedings of the National Academy of Sciences of the United States of America · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 3 countries.

Marta GaiDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy marta.gai@unito.it ferdinando.dicunto@unito.it.
Federico T BianchiDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
Cristiana VagnoniDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
Fiammetta VernìDepartment of Biology and Biotechnologies "C. Darwin", Sapienza, Università di Roma, Rome, Italy.
Silvia BonaccorsiDepartment of Biology and Biotechnologies "C. Darwin", Sapienza, Università di Roma, Rome, Italy.
Selina PasqueroDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
Gaia E BertoDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
Francesco SgròDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
Alessandra Ma ChiottoDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
Laura AnnaratoneDepartment of Medical Sciences, University of Turin, Turin, Italy.
Anna SapinoDepartment of Medical Sciences, University of Turin, Turin, Italy.
Anna BergoSan Raffaele Rett Research Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Nicoletta LandsbergerSan Raffaele Rett Research Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.ORCID 0000-0003-0820-3155
Jacqueline BondLeeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK.
Wieland B HuttnerMax-Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Ferdinando Di CuntoDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy marta.gai@unito.it ferdinando.dicunto@unito.it.ORCID 0000-0001-9367-6357
University of Turin · ITSan Raffaele University of Rome · ITSapienza University of Rome · ITMax Planck Institute of Molecular Cell Biology and Genetics · DEUniversity of Leeds · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Correct orientation of cell division is considered an important factor for the achievement of normal brain size, as mutations in genes that affect this process are among the leading causes of microcephaly. Abnormal spindle orientation is associated with reduction of the neuronal progenitor symmetric divisions, premature cell cycle exit, and reduced neurogenesis. This mechanism has been involved in microcephaly resulting from mutation of ASPM, the most frequently affected gene in autosomal recessive human primary microcephaly (MCPH), but it is presently unknown how ASPM regulates spindle orientation. In this report, we show that ASPM may control spindle positioning by interacting with citron kinase (CITK), a protein whose loss is also responsible for severe microcephaly in mammals. We show that the absence of CITK leads to abnormal spindle orientation in mammals and insects. In mouse cortical development, this phenotype correlates with increased production of basal progenitors. ASPM is required to recruit CITK at the spindle, and CITK overexpression rescues ASPM phenotype. ASPM and CITK affect the organization of astral microtubules (MT), and low doses of MT-stabilizing drug revert the spindle orientation phenotype produced by their knockdown. Finally, CITK regulates both astral-MT nucleation and stability. Our results provide a functional link between two established microcephaly proteins.

Indexed as

AnimalsBrainCalmodulin-Binding ProteinsCell LineDrosophilaDynactin ComplexFemaleGene Expression RegulationGene SilencingHeLa CellsHumansIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutMicrotubulesMitosisASPM protein, mouseCalmodulin-Binding Proteinscitron-kinaseDynactin ComplexIntracellular Signaling Peptides and ProteinsNerve Tissue ProteinsProtein Serine-Threonine Kinasesastral microtubulesasymmetric divisionmicrocephalymitotic spindle orientationneurogenesis

Identifiers

PMID27562601
PMCPMC5048379
OpenAlexW2511999035

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.