TY - JOUR
T1 - Connexin 32 increases the proliferative response of Schwann cells to neuregulin-1 (Nrg1)
AU - Freidin, Mona
AU - Asche, Samantha
AU - Bargiello, Thaddeus A.
AU - Bennett, Michael V.L.
AU - Abrams, Charles K.
PY - 2009/3/3
Y1 - 2009/3/3
N2 - Connexin 32 (Cx32), a gap junction protein, is found within the para-nodal region and Schmidt-Lanterman incisures of myelinating Schwann cells (SCs). In developing and regenerating peripheral nerves, pro-myelinating SCs express Cx32 mRNA and protein in conjunction with the expression of myelin specific genes. Neuregulin-1 (Nrg1), a member of the neuregulin family of growth factors, controls SC proliferation and differentiation depending on the cellular environment and the particular stage of SC maturation. Primary cultures of purified SCs from newborn mouse sciatic nerve were used to characterize both the role of Nrg1 in the expression of Cx32 and, conversely, the role of Cx32 in SC responsiveness to Nrg1. Glial growth factor 2, an isoform of Nrg1, up-regulated Cx32 in both proliferating and non-proliferating SCs. However, SCs from Cx32-KO mice exhibited a significantly smaller mitogenic response to glial growth factor 2. Electrical coupling between Cx32-KO SCs did not differ from that between WT SCs, indicating the presence of other connexins. These results suggest a link between Cx32 expression and Nrg1 regulation of SC proliferation that does not involve Cx32-mediated intercellular communication.
AB - Connexin 32 (Cx32), a gap junction protein, is found within the para-nodal region and Schmidt-Lanterman incisures of myelinating Schwann cells (SCs). In developing and regenerating peripheral nerves, pro-myelinating SCs express Cx32 mRNA and protein in conjunction with the expression of myelin specific genes. Neuregulin-1 (Nrg1), a member of the neuregulin family of growth factors, controls SC proliferation and differentiation depending on the cellular environment and the particular stage of SC maturation. Primary cultures of purified SCs from newborn mouse sciatic nerve were used to characterize both the role of Nrg1 in the expression of Cx32 and, conversely, the role of Cx32 in SC responsiveness to Nrg1. Glial growth factor 2, an isoform of Nrg1, up-regulated Cx32 in both proliferating and non-proliferating SCs. However, SCs from Cx32-KO mice exhibited a significantly smaller mitogenic response to glial growth factor 2. Electrical coupling between Cx32-KO SCs did not differ from that between WT SCs, indicating the presence of other connexins. These results suggest a link between Cx32 expression and Nrg1 regulation of SC proliferation that does not involve Cx32-mediated intercellular communication.
KW - CMTX
KW - Cell cycle
KW - Cx32 knockout
KW - Glial growth factor 2
KW - Myelin
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U2 - 10.1073/pnas.0813413106
DO - 10.1073/pnas.0813413106
M3 - Article
C2 - 19218461
AN - SCOPUS:62549145825
SN - 0027-8424
VL - 106
SP - 3567
EP - 3572
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 9
ER -