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Association of PSD‐95 with ErbB4 facilitates neuregulin signaling in cerebellar granule neurons in culture
Author(s) -
Xie Fang,
Padival Mallika,
Siegel Ruth E.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04182.x
Subject(s) - neuregulin , neuregulin 1 , erbb4 , microbiology and biotechnology , cyclin dependent kinase 5 , erbb , mapk/erk pathway , protein kinase a , signal transduction , kinase , protein subunit , biology , tropomyosin receptor kinase b , synaptic plasticity , gabab receptor , chemistry , mitogen activated protein kinase kinase , receptor , biochemistry , agonist , neurotrophic factors , gene , receptor tyrosine kinase
The growth factor neuregulin 1 (NRG) selectively induces an increase in the γ‐aminobutyric acid (GABA) A receptor β2 subunit protein in rat cerebellar granule neurons in culture. We previously demonstrated that NRG acts by triggering ErbB4 receptor phosphorylation and subsequent signaling through the mitogen‐activated kinase (MAPK), phosphatidyl inositol‐3 kinase (PI‐3K) and cyclin‐dependent kinase 5 (cdk5) pathways. In this report we show that the scaffolding protein, PSD‐95, plays a key role in mediating the effects of NRG and that reducing its level attenuates the NRG‐induced increase in β2 subunit expression. PSD‐95 appears to facilitate the effects of NRG through its association with ErbB4, an interaction that is augmented by NRG‐activated cdk signaling. Inhibition of cdk activity with roscovitine attenuates the association of PSD‐95 with ErbB4. The effects of cdk5 are not blocked by U0126, an inhibitor of MAPK signaling, indicating that cdk5 functions independently of cross‐talk with this pathway. These findings raise the possibility that NRG‐induced activation of cdk5 works in part by recruiting PSD‐95, a protein involved in regulating synaptic plasticity, to associate with ErbB4. This interaction may be a positive feedback loop that augments NRG signaling and its downstream effects on GABA A receptor β2 subunit expression.