Header

UZH-Logo

Maintenance Infos

Pincher-generated Nogo-A endosomes mediate growth cone collapse and retrograde signaling


Joset, A; Dodd, D A; Halegoua, S; Schwab, M E (2010). Pincher-generated Nogo-A endosomes mediate growth cone collapse and retrograde signaling. Journal of Cell Biology, 188(2):271-285.

Abstract

Nogo-A is one of the most potent myelin-associated inhibitors for axonal growth, regeneration, and plasticity in the adult central nervous system. The Nogo-A-specific fragment NogoDelta20 induces growth cone collapse, and inhibits neurite outgrowth and cell spreading by activating RhoA. Here, we show that NogoDelta20 is internalized into neuronal cells by a Pincher- and rac-dependent, but clathrin- and dynamin-independent, mechanism. Pincher-mediated macroendocytosis results in the formation of NogoDelta20-containing signalosomes that direct RhoA activation and growth cone collapse. In compartmentalized chamber cultures, NogoDelta20 is endocytosed into neurites and retrogradely transported to the cell bodies of dorsal root ganglion neurons, triggering RhoA activation en route and decreasing phosphorylated cAMP response element binding levels in cell bodies. Thus, Pincher-dependent macroendocytosis leads to the formation of Nogo-A signaling endosomes, which act both within growth cones and after retrograde transport in the cell body to negatively regulate the neuronal growth program.

Abstract

Nogo-A is one of the most potent myelin-associated inhibitors for axonal growth, regeneration, and plasticity in the adult central nervous system. The Nogo-A-specific fragment NogoDelta20 induces growth cone collapse, and inhibits neurite outgrowth and cell spreading by activating RhoA. Here, we show that NogoDelta20 is internalized into neuronal cells by a Pincher- and rac-dependent, but clathrin- and dynamin-independent, mechanism. Pincher-mediated macroendocytosis results in the formation of NogoDelta20-containing signalosomes that direct RhoA activation and growth cone collapse. In compartmentalized chamber cultures, NogoDelta20 is endocytosed into neurites and retrogradely transported to the cell bodies of dorsal root ganglion neurons, triggering RhoA activation en route and decreasing phosphorylated cAMP response element binding levels in cell bodies. Thus, Pincher-dependent macroendocytosis leads to the formation of Nogo-A signaling endosomes, which act both within growth cones and after retrograde transport in the cell body to negatively regulate the neuronal growth program.

Statistics

Citations

52 citations in Web of Science®
57 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

55 downloads since deposited on 05 Jan 2011
20 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:January 2010
Deposited On:05 Jan 2011 07:47
Last Modified:21 May 2016 16:30
Publisher:Rockefeller University Press
ISSN:0021-9525
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1083/jcb.200906089
PubMed ID:20083601

Download

Download PDF  'Pincher-generated Nogo-A endosomes mediate growth cone collapse and retrograde signaling'.
Preview
Filetype: PDF
Size: 3MB
View at publisher