Nestin Selectively Facilitates the Phosphorylation of the Lissencephaly-Linked Protein Doublecortin (DCX) by cdk5/p35 to Regulate Growth Cone Morphology and Sema3a Sensitivity in Developing Neurons.
Animals
COS Cells
Chlorocebus aethiops
Doublecortin Domain Proteins
Doublecortin Protein
Female
Growth Cones
/ metabolism
HEK293 Cells
Humans
Male
Mice
Mice, Knockout
Microtubule-Associated Proteins
/ metabolism
Nerve Tissue Proteins
/ metabolism
Nestin
/ metabolism
Neurogenesis
/ physiology
Neurons
/ metabolism
Neuropeptides
/ metabolism
Phosphorylation
Semaphorin-3A
/ metabolism
CDK5
DCX
axon guidance
growth cone
intermediate filaments
nestin
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
Titre abrégé: J Neurosci
Pays: United States
ID NLM: 8102140
Informations de publication
Date de publication:
06 05 2020
06 05 2020
Historique:
received:
17
10
2019
revised:
24
02
2020
accepted:
24
03
2020
pubmed:
11
4
2020
medline:
8
10
2020
entrez:
11
4
2020
Statut:
ppublish
Résumé
Nestin, an intermediate filament protein widely used as a marker of neural progenitors, was recently found to be expressed transiently in developing cortical neurons in culture and in developing mouse cortex. In young cortical cultures, nestin regulates axonal growth cone morphology. In addition, nestin, which is known to bind the neuronal cdk5/p35 kinase, affects responses to axon guidance cues upstream of cdk5, specifically, to Sema3a. Changes in growth cone morphology require rearrangements of cytoskeletal networks, and changes in microtubules and actin filaments are well studied. In contrast, the roles of intermediate filament proteins in this process are poorly understood, even in cultured neurons. Here, we investigate the molecular mechanism by which nestin affects growth cone morphology and Sema3a sensitivity. We find that nestin selectively facilitates the phosphorylation of the lissencephaly-linked protein doublecortin (DCX) by cdk5/p35, but the phosphorylation of other cdk5 substrates is not affected by nestin. We uncover that this substrate selectivity is based on the ability of nestin to interact with DCX, but not with other cdk5 substrates. Nestin thus creates a selective scaffold for DCX with activated cdk5/p35. Last, we use cortical cultures derived from
Identifiants
pubmed: 32273484
pii: JNEUROSCI.2471-19.2020
doi: 10.1523/JNEUROSCI.2471-19.2020
pmc: PMC7204086
doi:
Substances chimiques
DCX protein, human
0
Dcx protein, mouse
0
Doublecortin Domain Proteins
0
Doublecortin Protein
0
Microtubule-Associated Proteins
0
Nerve Tissue Proteins
0
Nestin
0
Neuropeptides
0
Semaphorin-3A
0
neuronal Cdk5 activator (p25-p35)
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3720-3740Subventions
Organisme : NIMH NIH HHS
ID : F30 MH112328
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS081674
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008136
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007863
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007544
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS097525
Pays : United States
Informations de copyright
Copyright © 2020 the authors.
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