Stimulated ErbB4 internalization is necessary for neuregulin signaling in neurons.
Neuregulin-1 (NRG1) plays an important role in neural development, synapse formation, and synaptic plasticity by activating ErbB receptor tyrosine kinases. Although ligand-induced endocytosis has been shown to be important for many receptor tyrosine kinases, whether NRG1 signaling depends on ErbB endocytosis remains controversial. Here, we provide evidence that ErbB4, a prominent ErbB protein in the brain, becomes internalized in NRG1-stimulated neurons. The induced ErbB4 endocytosis requires its kinase activity. Remarkably, inhibition of ErbB endocytosis attenuates NRG1-induced activation of Erk and Akt in neurons. These observations indicate a role of ErbB endocytosis in NRG1 signaling in neurons.
Liu
Yu
Y
Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA.
Tao
Yan-Mei
YM
Woo
Ran-Sook
RS
Xiong
Wen-Cheng
WC
Mei
Lin
L
D000818:Animals; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D020890:Neuregulin-1 / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; D015398:Signal Transduction / Q000502:physiology*
D066246:ErbB Receptors; D006023:Glycoproteins; D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; C483804:Erbb2 protein, rat; C587691:Erbb4 protein, rat