The signaling adaptor protein CD3zeta is a negative regulator of dendrite development in young neurons

Mol Biol Cell. 2008 Jun;19(6):2444-56. doi: 10.1091/mbc.e07-09-0947. Epub 2008 Mar 26.


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 CD3zeta, 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 CD3zeta is mainly expressed in neurons. Distribution of CD3zeta in developing cultured hippocampal neurons, as determined by immunofluorescence, indicates that CD3zeta is preferentially associated with the somatodendritic compartment as soon as the dendrites initiate their differentiation. At this stage, CD3zeta was selectively concentrated at dendritic filopodia and growth cones, actin-rich structures involved in neurite growth and patterning. siRNA-mediated knockdown of CD3zeta in cultured neurons or overexpression of a loss-of-function CD3zeta mutant lacking the tyrosine phosphorylation sites in the immunoreceptor tyrosine-based activation motifs (ITAMs) increased dendritic arborization. Conversely, activation of endogenous CD3zeta by a CD3zeta antibody reduced the size of the dendritic arbor. Altogether, our findings reveal a novel role for CD3zeta in the nervous system, suggesting its contribution to dendrite development through ITAM-based mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Antibodies / pharmacology
  • Brain / cytology
  • Brain / metabolism
  • CD3 Complex / metabolism*
  • COS Cells
  • Calcium / metabolism
  • Cells, Cultured
  • Chlorocebus aethiops
  • Dendrites / drug effects
  • Dendrites / enzymology
  • Dendrites / metabolism*
  • Growth Cones / drug effects
  • Growth Cones / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Male
  • Mutation / genetics
  • Neurites / drug effects
  • Neurites / enzymology
  • Phosphorylation / drug effects
  • Phosphotyrosine / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Pseudopodia / drug effects
  • Pseudopodia / metabolism
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Syk Kinase
  • ZAP-70 Protein-Tyrosine Kinase / metabolism


  • Actins
  • Adaptor Proteins, Signal Transducing
  • Antibodies
  • CD3 Complex
  • CD3 antigen, zeta chain
  • Intracellular Signaling Peptides and Proteins
  • RNA, Small Interfering
  • Phosphotyrosine
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, rat
  • ZAP-70 Protein-Tyrosine Kinase
  • Calcium