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Neuregulin 1β/erbB signalling in cardiac myocytes enhances integrin based myocyte‐matrix interactions via src
Author(s) -
Pentassuglia Laura,
Arteaga Carlos,
Sawyer Douglas
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.820.2
Subject(s) - myocyte , neuregulin , erbb , microbiology and biotechnology , integrin , proto oncogene tyrosine protein kinase src , neuregulin 1 , laminin , cardiac myocyte , chemistry , pi3k/akt/mtor pathway , extracellular matrix , signal transduction , biology , receptor , biochemistry
The Neuregulin‐1β (Nrg)‐erbB2/ErbB4 (E2/E4) system is critical for the heart and it is needed for myocyte survival in stress conditions. Nrg activates Src and FAK, both part of integrin signaling. Hyp.: Nrg signaling regulates myocyte matrix interactions, critical for coupling force generation to the extracellular matrix. Immunostaining of mouse hearts showed E4 and E2 are at intercalated discs and have a t‐tubule like striated pattern. Isolated myocytes were incubated 30 min or 24h with an E2 monoclonal antibody (Ab) or an E2 tyrosine kinase inhibitor (TKI). Western‐blot showed E2 TKI blocks activation of FAK, Erk1/2, and Akt by Nrg; Ab is a weak inhibitor. ErbB activation in myocyte‐matrix coupling was tested by plating myocytes onto untreated culture dishes spot‐coated with laminin, with or without Nrg (10ng/ml). After 30 minutes unattached cells were stained and counted. Attachment was enhanced 4‐fold by Nrg vs. laminin alone. Cells did not attach to Nrg coated plates in absence of laminin. Pre‐treatment of myocytes with E2 inhibitors did not prevent Nrg‐enhanced attachment; pre‐treated with Src inhibitor PP2 (10 μM) Nrg effect was inhibited. Nrg‐1β treatment of cardiac myocytes enhances integrin mediated myocyte‐matrix coupling via Src dependent signalling. This appears to be E2 independent pathway, involving E4 signaling, supported by e4 localization to the intercalated disks in vivo. Support by SNSF, NIH.