Differential localization of ErbB receptor ensembles influences their signaling in hippocampal neurons.

Published

Journal Article

Our studies indicate that ErbB complexes participate in both survival and synaptic plasticity signals of hippocampal neurons but in a manner that depends on the subcellular localization of the receptor ensembles. Using dissociated hippocampal cultures, we found that neurons, rather than glial cells, are the primary targets of ErbB receptor ligands such as epidermal growth factor and heregulin. Further investigation demonstrated that ErbB receptors distribute differentially in hippocampal neurons with the epidermal growth factor receptor confined to neural cell bodies and the p185(c-neu) and ErbB4 receptors distributed to both neural soma and neurites. Activation of ErbB receptor and downstream signaling molecules were observed in neurites only after heregulin stimulation. The receptor complex which mediated neurite located signals was the p185(c-neu)/ErbB4 heterodimer. Colocalization of p185(c-neu), but not epidermal growth factor receptor, with postsynaptic density protein 95 suggests that the heregulin signaling contributes to synapse specific activities. However, the epidermal growth factor receptor complex mediates physiological survival signals, as neuronal survival was enhanced by epidermal growth factor, rather than heregulin. Collectively, these studies indicate that different ErbB ensembles localize to different locations on the neuron to mediate distinct signals and functions.

Full Text

Duke Authors

Cited Authors

  • Chen, J; Tseng, HC; Dichter, MA; Zhang, H; Greene, MI

Published Date

  • September 2005

Published In

Volume / Issue

  • 24 / 9

Start / End Page

  • 553 - 562

PubMed ID

  • 16153156

Pubmed Central ID

  • 16153156

Electronic International Standard Serial Number (EISSN)

  • 1557-7430

International Standard Serial Number (ISSN)

  • 1044-5498

Digital Object Identifier (DOI)

  • 10.1089/dna.2005.24.553

Language

  • eng