Connexin 32 increases the proliferative response of Schwann cells to neuregulin-1 (Nrg1).
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.
Freidin
Mona
M
Department of Neurology, State University of New York Downstate at Brooklyn, Brooklyn NY 10021, USA. mona.freidin@downstate.edu
Asche
Samantha
S
Bargiello
Thaddeus A
TA
Bennett
Michael V L
MV
Abrams
Charles K
CK
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017630:Connexins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D020890:Neuregulin-1 / Q000378:metabolism* / Q000494:pharmacology; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D020890:Neuregulin-1; D000097002:Gap Junction beta-1 Protein