Plk4 Regulates Centriole Asymmetry and Spindle Orientation in Neural Stem Cells.
Animals
Cdh1 Proteins
/ genetics
Cell Cycle
Cells, Cultured
Centrioles
/ physiology
Centrosome
/ metabolism
Drosophila Proteins
/ genetics
Drosophila melanogaster
/ genetics
Female
Male
Neural Stem Cells
/ cytology
Phosphorylation
Protein Serine-Threonine Kinases
/ genetics
Spindle Apparatus
/ physiology
Plk4
Spd2
centrosome positioning
centrosomes
spindle orientation
symmetry breaking
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
01 07 2019
01 07 2019
Historique:
received:
13
12
2017
revised:
08
03
2019
accepted:
23
04
2019
pubmed:
28
5
2019
medline:
25
1
2020
entrez:
28
5
2019
Statut:
ppublish
Résumé
Defects in mitotic spindle orientation (MSO) disrupt the organization of stem cell niches impacting tissue morphogenesis and homeostasis. Mutations in centrosome genes reduce MSO fidelity, leading to tissue dysplasia and causing several diseases such as microcephaly, dwarfism, and cancer. Whether these mutations perturb spindle orientation solely by affecting astral microtubule nucleation or whether centrosome proteins have more direct functions in regulating MSO is unknown. To investigate this question, we analyzed the consequences of deregulating Plk4 (the master centriole duplication kinase) activity in Drosophila asymmetrically dividing neural stem cells. We found that Plk4 functions upstream of MSO control, orchestrating centriole symmetry breaking and consequently centrosome positioning. Mechanistically, we show that Plk4 acts through Spd2 phosphorylation, which induces centriole release from the apical cortex. Overall, this work not only reveals a role for Plk4 in regulating centrosome function but also links the centrosome biogenesis machinery with the MSO apparatus.
Identifiants
pubmed: 31130353
pii: S1534-5807(19)30333-8
doi: 10.1016/j.devcel.2019.04.036
pmc: PMC6614718
pii:
doi:
Substances chimiques
Cdh1 Proteins
0
Drosophila Proteins
0
SPD-2 protein, Drosophila
0
fzr protein, Drosophila
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
Sak protein, Drosophila
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11-24.e10Subventions
Organisme : NCI NIH HHS
ID : P30 CA023074
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM110166
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM126035
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM136265
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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