DIAPH3 deficiency links microtubules to mitotic errors, defective neurogenesis, and brain dysfunction.
Animals
Behavior, Animal
Cell Cycle Proteins
/ genetics
Cell Line, Tumor
Cerebral Cortex
/ metabolism
Feeding Behavior
Formins
/ deficiency
Gene Expression Regulation, Developmental
Genotype
Humans
Locomotion
Maze Learning
Mice
Mice, Knockout
Microtubules
/ genetics
Mitosis
NIH 3T3 Cells
Neurogenesis
Neurons
/ metabolism
Phenotype
Social Behavior
Spindle Apparatus
/ genetics
Astrin
MTOC
mDia2
malformation of cortical development
mouse
neuroscience
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
26 04 2021
26 04 2021
Historique:
received:
10
08
2020
accepted:
23
04
2021
pubmed:
27
4
2021
medline:
28
10
2021
entrez:
26
4
2021
Statut:
epublish
Résumé
Diaphanous (DIAPH) three (DIAPH3) is a member of the formin proteins that have the capacity to nucleate and elongate actin filaments and, therefore, to remodel the cytoskeleton. DIAPH3 is essential for cytokinesis as its dysfunction impairs the contractile ring and produces multinucleated cells. Here, we report that DIAPH3 localizes at the centrosome during mitosis and regulates the assembly and bipolarity of the mitotic spindle. DIAPH3-deficient cells display disorganized cytoskeleton and multipolar spindles. DIAPH3 deficiency disrupts the expression and/or stability of several proteins including the kinetochore-associated protein SPAG5. DIAPH3 and SPAG5 have similar expression patterns in the developing brain and overlapping subcellular localization during mitosis. Knockdown of SPAG5 phenocopies DIAPH3 deficiency, whereas its overexpression rescues the DIAHP3 knockdown phenotype. Conditional inactivation of
Identifiants
pubmed: 33899739
doi: 10.7554/eLife.61974
pii: 61974
pmc: PMC8102060
doi:
pii:
Substances chimiques
Cell Cycle Proteins
0
Formins
0
Spag5 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© 2021, Lau et al.
Déclaration de conflit d'intérêts
EL, DD, GC, NR, RS, YJ, MA, OS, NT, PG No competing interests declared, FT Reviewing editor, eLife
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