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Vol. 19, Issue 6, 2444-2456, June 2008

This Article Full Text Full Text (PDF) All Versions of this Article: E07-09-0947v1 19/6/2444    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Baudouin, S. J. Articles by Boudin, H. PubMed PubMed Citation Articles by Baudouin, S. J. Articles by Boudin, H.

The Signaling Adaptor Protein CD3 Is a Negative Regulator of Dendrite Development in Young Neurons

Stéphane J. Baudouin^*,,, Julie Angibaud^*,,, Gildas Loussouarn^,,||, Virginie Bonnamain^*,,, Akihiro Matsuura^¶, Miyuki Kinebuchi^¶, Philippe Naveilhan^*,,, and Hélène Boudin^*,,

INSERM, *U643 and U915, Nantes, F44000 France; CHU Nantes, Institut de Transplantation et de Recherche en Transplantation, Nantes, F44000 France; Université de Nantes, Faculté de Médecine, Nantes, F44000 France; ^||Centre National de la Recherche Scientifique, ERL3147, F-44000, France; and ^¶Department of Pathology, Fujita Health University School of Medicine, Aichi, 470-1192, Japan

Submitted September 20, 2007; Revised March 17, 2008; Accepted March 19, 2008
Monitoring Editor: Erika Holzbaur

A novel idea is emergxsing that a large molecular repertoire is common to the nervous and immune systems, which might reflect the existence of novel neuronal functions for immune molecules in the brain. Here, we show that the transmembrane adaptor signaling protein CD3, first described in the immune system, has a previously uncharacterized role in regulating neuronal development. Biochemical and immunohistochemical analyses of the rat brain and cultured neurons showed that CD3 is mainly expressed in neurons. Distribution of CD3 in developing cultured hippocampal neurons, as determined by immunofluorescence, indicates that CD3 is preferentially associated with the somatodendritic compartment as soon as the dendrites initiate their differentiation. At this stage, CD3 was selectively concentrated at dendritic filopodia and growth cones, actin-rich structures involved in neurite growth and patterning. siRNA-mediated knockdown of CD3 in cultured neurons or overexpression of a loss-of-function CD3 mutant lacking the tyrosine phosphorylation sites in the immunoreceptor tyrosine-based activation motifs (ITAMs) increased dendritic arborization. Conversely, activation of endogenous CD3 by a CD3 antibody reduced the size of the dendritic arbor. Altogether, our findings reveal a novel role for CD3 in the nervous system, suggesting its contribution to dendrite development through ITAM-based mechanisms.

Address correspondence to: Hélène Boudin (helene.boudin{at}univ-nantes.fr)

Abbreviations used: ITAM, immunoreceptor tyrosine-based activation motif; TCR, T-cell receptor; DIV, day in vitro.