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PMID: 12716924 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Ligand-dependent recruitment of the ErbB4 signaling complex into neuronal lipid rafts.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 23 ·No. 8 ·2003-04-15 ·Pages 3164-75

Ma L, Huang YZ, Pitcher GM, Valtschanoff JG, Ma YH, Feng LY, Lu B, Xiong WC, Salter MW, Weinberg RJ, Mei L

Abstract

Neuregulin (NRG) regulates synapse formation and synaptic plasticity, but little is known about the regulation of NRG signaling at synapses. Here we show that the NRG receptor ErbB4 was localized in anatomically defined postsynaptic densities in the brain. In cultured cortical neurons, ErbB4 was recruited to the neuronal lipid raft fraction after stimulation by NRG. Along with ErbB4, adaptor proteins Grb2 and Shc were translocated to lipid rafts by NRG stimulation. In transfected human embryonic kidney 293 cells, the partitioning of ErbB4 into a detergent-insoluble fraction that includes lipid rafts was increased by PSD-95 (postsynaptic density-95), through interaction of the ErbB4 C terminus with the PDZ [PSD-95/Discs large/zona occludens-1] domains of PSD-95. Disruption of lipid rafts inhibited NRG-induced activation of Erk and prevented NRG-induced blockade of induction of long-term potentiation at hippocampal CA1 synapses. Thus, our results indicate that NRG stimulation causes translocation of ErbB4 into lipid rafts and that lipid rafts are necessary for signaling by ErbB4.

MeSH Terms
Adaptor Proteins, Signal Transducing Adaptor Proteins, Vesicular Transport Animals Brain Chemistry Cells, Cultured Disks Large Homolog 4 Protein ErbB Receptors/metabolism GRB2 Adaptor Protein Humans Intracellular Signaling Peptides and Proteins Kidney/cytology,metabolism Ligands Long-Term Potentiation/physiology Macromolecular Substances Male Membrane Microdomains/metabolism,ultrastructure Membrane Proteins Microscopy, Immunoelectron Mitogen-Activated Protein Kinases/metabolism Nerve Tissue Proteins/metabolism,ultrastructure Neuregulins/metabolism,pharmacology Neuronal Plasticity/physiology Neurons/drug effects,metabolism,ultrastructure Poisson Distribution Protein Structure, Tertiary/physiology Protein Transport/physiology Proteins/metabolism Rats Rats, Sprague-Dawley Receptor, ErbB-4 Shc Signaling Adaptor Proteins Signal Transduction/physiology Src Homology 2 Domain-Containing, Transforming Protein 1
Chemicals
Adaptor Proteins, Signal Transducing Adaptor Proteins, Vesicular Transport Disks Large Homolog 4 Protein Dlg4 protein, rat GRB2 Adaptor Protein GRB2 protein, human Grb2 protein, rat Intracellular Signaling Peptides and Proteins Ligands Macromolecular Substances Membrane Proteins Nerve Tissue Proteins Neuregulins Proteins SHC1 protein, human Shc Signaling Adaptor Proteins Shc1 protein, rat Src Homology 2 Domain-Containing, Transforming Protein 1 postsynaptic density proteins ERBB4 protein, human ErbB Receptors Erbb4 protein, rat Receptor, ErbB-4 Mitogen-Activated Protein Kinases
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Ma Li
Department of Neurobiology, University of Alabama at Birmingham, Civitan International Research Center, Birmingham, Alabama 35294-0021, USA.
Huang Yang Z
Pitcher Graham M
Valtschanoff Juli G
Ma Ying H
Feng Lin Y
Lu Bai
Xiong Wen C
Salter Michael W
Weinberg Richard J
Mei Lin
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2003-04-15
Pages
3164-75
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6742330
Subset
IM
Grants
NINDS NIH HHS · R01 NS039444 · United States
NINDS NIH HHS · R01 NS040480 · United States
NINDS NIH HHS · NS39444 · United States
NINDS NIH HHS · NS40480 · United States
External Links
PubMed source PMC Full Text View journal details
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