A pair of E3 ubiquitin ligases compete to regulate filopodial dynamics and axon guidance

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 res...

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Vydáno v:	The Journal of cell biology Ročník 219; číslo 1
Hlavní autoři:	Boyer, Nicholas P, McCormick, Laura E, Menon, Shalini, Urbina, Fabio L, Gupton, Stephanie L
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 06.01.2020
Témata:	Animals Axon Guidance - physiology Cell Adhesion Molecules - genetics Cell Adhesion Molecules - metabolism Cytoskeletal Proteins - physiology Female HEK293 Cells Humans Male Mice Mice, Inbred C57BL Mice, Knockout Microfilament Proteins - genetics Microfilament Proteins - metabolism Nerve Tissue Proteins - physiology Netrin-1 - genetics Netrin-1 - metabolism Neurons - cytology Neurons - metabolism Phosphoproteins - genetics Phosphoproteins - metabolism Pseudopodia - physiology Tripartite Motif Proteins - physiology Ubiquitin - metabolism Ubiquitin-Protein Ligases - physiology Ubiquitination
ISSN:	1540-8140, 1540-8140
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1540-8140 1540-8140
DOI:	10.1083/jcb.201902088