Compartmentalized NRG signaling and PDZ domain-containing proteins in synapse structure and function.

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Agrin, Animals, COS Cells, Cell Compartmentation, Humans, Immunohistochemistry, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Mitogen-Activated Protein Kinases, Muscle Cells, Muscle Fibers, Skeletal, Nerve Tissue Proteins, Neuregulin-1, Neuromuscular Junction, Neuropeptides, Nuclear Proteins, Phosphorylation, Protein Structure, Tertiary, RNA, Messenger, Receptor, Epidermal Growth Factor, Receptors, Cholinergic, Signal Transduction, Synaptic Transmission, Transcription Factors, Tyrosine
Int. J. Dev. Neurosci.
Date: Aug. 15, 2002
Download Curated Data For This Publication
8602
Switch View:
  • Interactions 1