Erbin is a protein concentrated at postsynaptic membranes that interacts with PSD-95.
Neuregulin is a factor essential for synapse-specific transcription of acetylcholine receptor genes at the neuromuscular junction. Its receptors, ErbB receptor tyrosine kinases, are localized at the postjunctional membrane presumably to ensure localized signaling. However, the molecular mechanisms underlying synaptic localization of ErbBs are unknown. Our recent studies indicate that ErbB4 interacts with postsynaptic density (PSD)-95 (SAP90), a PDZ domain-containing protein that does not interact with ErbB2 or ErbB3. Using as bait the ErbB2 C terminus, we identified Erbin, another PDZ domain-containing protein that interacts specifically with ErbB2. Erbin is concentrated in postsynaptic membranes at the neuromuscular junction and in the central nervous system, where ErbB2 is concentrated. Expression of Erbin increases the amount of ErbB2 labeled by biotin in transfected cells, suggesting that Erbin is able to increase ErbB2 surface expression. Furthermore, we provide evidence that Erbin interacts with PSD-95 in both transfected cells and synaptosomes. Thus ErbB proteins can interact with a network of PDZ domain-containing proteins. This interaction may play an important role in regulation of neuregulin signaling and/or subcellular localization of ErbB proteins.
Departments of Neurobiology, University of Alabama at Birmingham, School of Medicine, Birmingham, Alabama 35294, USA.
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Huang
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Wang
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Xiong
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Mei
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001710:Biotin / Q000378:metabolism; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D066246:ErbB Receptors / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009132:Muscles / Q000196:embryology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000378:metabolism; D066247:Receptor, ErbB-4; D015398:Signal Transduction; D013347:Subcellular Fractions; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D001710:Biotin; D002352:Carrier Proteins; D018076:DNA, Complementary; D000076122:Disks Large Homolog 4 Protein; D066246:ErbB Receptors; D005656:Fungal Proteins; D005982:Glutathione Transferase; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C501444:DLG4 protein, human; C501449:Dlg4 protein, rat; C413364:ERBIN protein, human; C033652:postsynaptic density proteins; C587689:ERBB4 protein, human; C587691:Erbb4 protein, rat