Neuregulin-induced expression of the acetylcholine receptor requires endocytosis of ErbB receptors.
Neuregulin-induced expression of the acetylcholine receptor (AChR) contributes to high concentration of the receptor at the neuromuscular junction (NMJ). Neuregulin-1 activates ErbB tyrosine kinases and subsequently intracellular kinases including Erk that is required for induced AChR expression. Recent studies demonstrate that ligand-induced internalization may regulate signaling of various receptor tyrosine kinases. However, the role of induced ErbB endocytosis in regulating AChR expression was unclear. Here we provide evidence that ErbB tyrosine kinases became rapidly internalized in response to neuregulin. The internalization required the kinase activity of ErbB proteins and involved a clathrin-dependent endocytic pathway. Moreover, neuregulin-induced Erk activation and AChR expression were attenuated when ErbB endocytosis was blocked. These results indicate that ErbB proteins undergo endocytosis in response to neuregulin, and this process is required for neuregulin signaling and induced AChR expression.
Yang
Xiao-Li
XL
Department of Neurobiology, University of Alabama at Birmingham, Civitan International Research Center, Birmingham, AL 35294, USA.
Huang
Yang Z
YZ
Xiong
Wen C
WC
Mei
Lin
L
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D008024:Ligands; D020890:Neuregulin-1 / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000378:metabolism; D066247:Receptor, ErbB-4; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D022161:Transport Vesicles / Q000378:metabolism
D002966:Clathrin; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D008024:Ligands; D020890:Neuregulin-1; D010770:Phosphotransferases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D011978:Receptors, Nicotinic; C587689:ERBB4 protein, human; C587691:Erbb4 protein, rat