Dataset Information

Connexin 32 increases the proliferative response of Schwann cells to neuregulin-1 (Nrg1).

ABSTRACT: 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.

SUBMITTER: Freidin M

PROVIDER: S-EPMC2651262 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Connexin 32 increases the proliferative response of Schwann cells to neuregulin-1 (Nrg1).

Freidin Mona M Asche Samantha S Bargiello Thaddeus A TA Bennett Michael V L MV Abrams Charles K CK

Proceedings of the National Academy of Sciences of the United States of America 20090213 9

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 ...[more]

PMID: 19218461

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Project description:Connexins (Cx) are primary components of gap junctions that selectively allow molecules to be exchanged between adjacent cells, regulating multiple cellular functions. Along with their channel forming functions, connexins play a variety of roles in different stages of tumorigenesis and their roles in tumor initiation and progression is isoform- and tissue-specific. While Cx26 and Cx43 were downregulated during breast tumorigenesis, Cx32 was accumulated in the cytoplasm of the cells in lymph node metastasis of breast cancers and Cx32 was further upregulated in metastasis. Cx32's effect on cell proliferation, gap junctional communication, hemichannel activity, cellular motility and epithelial-to-mesenchymal transition (EMT) were investigated by overexpressing Cx32 in Hs578T and MCF7 breast cancer cells. Additionally, the expression and localization of Cx26 and Cx43 upon Cx32 overexpression were examined by Western blot and immunostaining experiments, respectively. We observed that MCF7 cells had endogenous Cx32 while Hs578T cells did not and when Cx32 was overexpressed in these cells, it caused a significant increase in the percentages of Hs578T cells at the S phase in addition to increasing their proliferation. Further, while Cx32 overexpression did not induce hemichannel activity in either cell, it decreased gap junctional communication between Hs578T cells. Additionally, Cx32 was mainly observed in the cytoplasm in both cells, where it did not form gap junction plaques but Cx32 overexpression reduced Cx43 levels without affecting Cx26. Moreover, migration and invasion potentials of Hs578T and migration in MCF7 were reduced upon Cx32 overexpression. Finally, the protein level of mesenchymal marker N-cadherin decreased while epithelial marker ZO-1 and E-cadherin increased in Hs578T cells. We observed that Cx32 overexpression altered cell proliferation, communication, migration and EMT in Hs578T, suggesting a tumor suppressor role in these cells while it had minor effects on MCF7 cells.

Dataset Information

Connexin 32 increases the proliferative response of Schwann cells to neuregulin-1 (Nrg1).

Publications

Connexin 32 increases the proliferative response of Schwann cells to neuregulin-1 (Nrg1).

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