Ubiquitination of the GTPase Rap1B by the ubiquitin ligase Smurf2 is required for the establishment of neuronal polarity

The development of a polarised morphology with multiple dendrites and a single axon is an essential step in the differentiation of neurons. The establishment of neuronal polarity is directed by the sequential activity of the GTPases Rap1B and Cdc42. Rap1B is initially present in all neurites of unpo...

Full description

Saved in:
Bibliographic Details
Published in:The EMBO journal 2007-03, Vol.26 (5), p.1410-1422
Main Authors: Schwamborn, Jens C, Müller, Myriam, Becker, Annemarie HM, Püschel, Andreas W
Format: Article
Language:English
Subjects:
Animals
Axons - metabolism
Biochemistry
Biotechnology
Blotting, Western
cdc42 GTP-Binding Protein - genetics
cdc42 GTP-Binding Protein - metabolism
Cell Differentiation - drug effects
Cell Polarity - drug effects
Cells, Cultured
Dendrites
GTPase
HeLa Cells
Humans
Immunoprecipitation
Lactones - pharmacology
Models, Biological
Molecular biology
Mutation
Neurites - drug effects
Neurites - metabolism
neuronal polarity
Neurons
Neurons - cytology
Neurons - drug effects
Neurons - metabolism
Neurosciences
Protein Binding
Proteins
rap GTP-Binding Proteins - genetics
rap GTP-Binding Proteins - metabolism
Rats
RNA Interference
Signal transduction
ubiquitin
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
Ubiquitins - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The development of a polarised morphology with multiple dendrites and a single axon is an essential step in the differentiation of neurons. The establishment of neuronal polarity is directed by the sequential activity of the GTPases Rap1B and Cdc42. Rap1B is initially present in all neurites of unpolarised neurons, but becomes restricted to the tip of a single process during the establishment of neuronal polarity where it specifies axonal identity. Here, we show that the ubiquitin ligases Smad ubiquitination regulatory factor-1 (Smurf1) and Smurf2 are essential for neurite growth and neuronal polarity, respectively, and regulate the GTPases Rho and Rap1B in hippocampal neurons. Smurf2 is required for the restriction of Rap1B to a single neurite. Smurf2 ubiquitinates inactive Rap1B and initiates its degradation through the ubiquitin/proteasome pathway (UPS). Degradation of Rap1B restricts it to a single neurite and thereby ensures that neurons extend a single axon.
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7601580