Regulation of ErbB4 via stimulation of GPCR for neurotransmitter and synaptic functions

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ErbB4 belongs to the ErbB protein family and is abundantly expressed in neurons. It plays important roles in synaptic functions. In the previous work, we found that gonadotropin-releasing hormone (GnRH) transactivated ErbB4 in hypothalamic neurons (GT1-7 cells). We also found that the higher concentration of GnRH induced the cleavage of ErbB4. In the present study, we examined the molecular mechanisms of GnRH-induced activation and cleavage of ErbB4. ErbB4 activation was measured by the ErbB4-induced activation of ERK. We found that Gq/11 proteins, PKC, PKD, Fyn and PYK2 were involved in the activation of ErbB4. In contrast, only Gq/11 proteins and PKC, but not PKD, Fyn and PYK2, were involved in the cleavage of ErbB4. These results suggest that the activation and cleavage of ErbB4 are induced by different molecular mechanisms after PKC activation.