title: Compartmentalized NRG signaling and PDZ domain-containing proteins in synapse structure and function.
abstract: The synapse-specific synthesis of the acetylcholine receptor (AChR) is mediated by multiple mechanisms including compartmentalized signaling induced by neuregulin (NRG). This paper presents evidence that NRG receptors--ErbB receptor tyrosine kinases interact with distinct PDZ domain-containing proteins that are localized at the neuromuscular junction (NMJ). ErbB4 associates with the PSD-95 (also known as SAP90)-family members including PSD-95, SAP97, and SAP102 whereas ErbB2 interacts with Erbin and PICK1. Although, ErbB kinases are concentrated at the NMJ, they are not colocalized with the AChR in cultured muscle cells even in the presence of agrin. Co-expression of PSD-95 causes ErbB4 to form clusters in COS cells. We propose that PDZ domain-containing proteins play a role in anchoring ErbB proteins at the neuromuscular junction, and/or mediating downstream signaling pathways. Such mechanisms could be important for the maintenance and function of the synapse.
authors.affiliation: Department of Neurobiology, Pathology, Physical Medicine and Rehabilitation, University of Alabama at Birmingham, 35294-0021, USA.
authors.forename: Yang Z
authors.initials: YZ
authors.lastname: Huang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Sandra
authors.initials: S
authors.lastname: Won
authors.forename: Zhen G
authors.initials: ZG
authors.lastname: Luo
authors.forename: Wen C
authors.initials: WC
authors.lastname: Xiong
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D018171:Agrin / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D002451:Cell Compartmentation / Q000502:physiology; D000074288:Discs Large Homolog 1 Protein; D000076122:Disks Large Homolog 4 Protein; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032342:Muscle Cells / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020890:Neuregulin-1 / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D009687:Nuclear Proteins; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D066247:Receptor, ErbB-4; D011950:Receptors, Cholinergic / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D014157:Transcription Factors; D014443:Tyrosine / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018171:Agrin; C513314:DLG1 protein, human; C116869:DLG3 protein, human; C501444:DLG4 protein, human; D000074288:Discs Large Homolog 1 Protein; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D009479:Neuropeptides; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D014157:Transcription Factors; C033652:postsynaptic density proteins; D014443:Tyrosine; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4; D020928:Mitogen-Activated Protein Kinases