Article
- The EMBO Journal (2007) 26, 1410 - 1422
- doi:10.1038/sj.emboj.7601580
Published online: 22 February 2007
Subject Categories:
Ubiquitination of the GTPase Rap1B by the ubiquitin ligase Smurf2 is required for the establishment of neuronal polarity
Jens C Schwamborn1,a, Myriam Müller1, Annemarie HM Becker1 and Andreas W Püschel1
- Abteilung Molekularbiologie, Institut für Allgemeine Zoologie und Genetik, Westfälische Wilhelms-Universität Münster, Münster, Germany
Correspondence to:
Andreas W Püschel,
Abteilung Molekularbiologie, Institut für Allgemeine Zoologie und Genetik, Westfälische Wilhelms-Universität Münster, Schlo
platz 5, 48149 Münster, Germany. Tel.: +49 2518323841; Fax: +49 2518324723; E-mail: apuschel@uni-muenster.de
aPresent address: IMBA—Institute of Molecular Biotechnology, Dr Bohrgasse 3, 1030 Vienna, Austria
Received 20 July 2006; Accepted 9 January 2007
Abstract
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.
Keywords:
- GTPase,
- neuronal polarity,
- ubiquitin
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