A pair of E3 ubiquitin ligases compete to regulate filopodial dynamics and axon guidance.
Animals
Axon Guidance
/ physiology
Cell Adhesion Molecules
/ genetics
Cytoskeletal Proteins
/ physiology
Female
HEK293 Cells
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microfilament Proteins
/ genetics
Nerve Tissue Proteins
/ physiology
Netrin-1
/ genetics
Neurons
/ cytology
Phosphoproteins
/ genetics
Pseudopodia
/ physiology
Tripartite Motif Proteins
/ physiology
Ubiquitin
/ metabolism
Ubiquitin-Protein Ligases
/ physiology
Ubiquitination
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
06 01 2020
06 01 2020
Historique:
received:
14
02
2019
revised:
25
09
2019
accepted:
25
10
2019
entrez:
11
12
2019
pubmed:
11
12
2019
medline:
28
7
2020
Statut:
ppublish
Résumé
Appropriate axon guidance is necessary to form accurate neuronal connections. Axon guidance cues that stimulate cytoskeletal reorganization within the growth cone direct axon navigation. Filopodia at the growth cone periphery have long been considered sensors for axon guidance cues, yet how they respond to extracellular cues remains ill defined. Our previous work found that the filopodial actin polymerase VASP and consequently filopodial stability are negatively regulated via nondegradative TRIM9-dependent ubiquitination. Appropriate VASP ubiquitination and deubiquitination are required for axon turning in response to the guidance cue netrin-1. Here we show that the TRIM9-related protein TRIM67 outcompetes TRIM9 for interacting with VASP and antagonizes TRIM9-dependent VASP ubiquitination. The surprising antagonistic roles of two closely related E3 ubiquitin ligases are required for netrin-1-dependent filopodial responses, axon turning and branching, and fiber tract formation. We suggest a novel model in which coordinated regulation of VASP ubiquitination by a pair of interfering ligases is a critical element of VASP dynamics, filopodial stability, and axon guidance.
Identifiants
pubmed: 31820781
pii: 132731
doi: 10.1083/jcb.201902088
pmc: PMC7039193
pii:
doi:
Substances chimiques
Cell Adhesion Molecules
0
Cytoskeletal Proteins
0
Microfilament Proteins
0
Nerve Tissue Proteins
0
Ntn1 protein, mouse
0
Phosphoproteins
0
TRIM67 protein, mouse
0
Tripartite Motif Proteins
0
Ubiquitin
0
vasodilator-stimulated phosphoprotein
0
Netrin-1
158651-98-0
Trim9 protein, mouse
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM135160
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM108970
Pays : United States
Organisme : NINDS NIH HHS
ID : F31 NS096823
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016086
Pays : United States
Organisme : NINDS NIH HHS
ID : F31 NS113381
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS045892
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD079124
Pays : United States
Organisme : NINDS NIH HHS
ID : F31 NS103586
Pays : United States
Organisme : NINDS NIH HHS
ID : T32 NS007431
Pays : United States
Informations de copyright
© 2019 Boyer et al.
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