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Axonal neuregulin signals cells of the oligodendrocyte lineage through activation of HER4 and Schwann cells through HER2 and HER3.

Vartanian T, Goodearl A, Viehöver A, Fischbach G - J. Cell Biol. (1997)

Bottom Line: We have found that oligodendrocite-type II astrocyte (O2A) progenitor cells and mature oligodendrocytes express HER2 and HER4 but no HER3.Coimmunoprecipitation experiments indicate that receptor activation in Schwann cells results in the formation of HER2:HER3 heterodimers.The use of unique neuregulin receptor combinations in oligodendrocytes and Schwann cells likely results in recruitment of different signaling pathways and thus provides a basis for different biological responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.

ABSTRACT
We are interested in the signaling between axons and glia that leads to myelination and maintenance of the myelin internode, and we have focused on the role of neuregulins and their receptors. Neuregulins are a family of ligands that includes heregulin, neu differentiation factor, glial growth factor, and the acetylcholine receptor-inducing activity. Three signal transducing transmembrane receptors for neuregulins, which bear significant homology to the EGF receptor, are currently known: HER2 (erbB2), HER3 (erbB3), and HER4 (erbB4). We have found that oligodendrocite-type II astrocyte (O2A) progenitor cells and mature oligodendrocytes express HER2 and HER4 but no HER3. Schwann cells express HER2 and HER3 but little HER4. In O2A progenitor cells and oligodendrocytes, recombinant neuregulin induces the rapid tyrosine phosphorylation of only HER4. HER2 is not phosphorylated in cells of the oligodendrocyte lineage, but a physical interaction between HER2 and HER4 was detected in coimmunoprecipitation experiments. In Schwann cells, neuregulin induces the phosphorylation of both HER2 and HER3. Coimmunoprecipitation experiments indicate that receptor activation in Schwann cells results in the formation of HER2:HER3 heterodimers. Neuregulin localized immunocytochemically was present on neurites of cultured dorsal root ganglion neurons, and it was released into the medium in a form that promoted receptor tyrosine phosphorylation. Neuregulins therefore meet important criteria expected of molecules involved in axonal-glial signaling. The use of unique neuregulin receptor combinations in oligodendrocytes and Schwann cells likely results in recruitment of different signaling pathways and thus provides a basis for different biological responses.

Show MeSH
Distinct neuregulin receptor expression by CNS and  PNS glial cells. Primary cultures of astrocytes, O2A progenitor cells,  oligodendrocytes, and Schwann cells were prepared as described.  Cell lysates containing 10 μg of protein were resolved on 4–15%  gradient polyacrylamide gels and probed with HER2, HER3, or  HER4 antibodies. Cells in the oligodendrocyte lineage express  HER2 and HER4, Schwann cells express HER2 and HER3, and  astrocytes express HER2, HER3, and HER4.
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Figure 2: Distinct neuregulin receptor expression by CNS and PNS glial cells. Primary cultures of astrocytes, O2A progenitor cells, oligodendrocytes, and Schwann cells were prepared as described. Cell lysates containing 10 μg of protein were resolved on 4–15% gradient polyacrylamide gels and probed with HER2, HER3, or HER4 antibodies. Cells in the oligodendrocyte lineage express HER2 and HER4, Schwann cells express HER2 and HER3, and astrocytes express HER2, HER3, and HER4.

Mentions: Western blot analysis confirmed the presence of significant levels of HER2 and HER4 and the absence of HER3 in total lysates of cultured O2A progenitor cells and oligodendrocytes (Fig. 2). In contrast to cells in the oligodendrocyte lineage, astrocytes express all three neuregulin receptors (Fig. 2). Unlike cells in the oligodendrocyte lineage, Schwann cells express large amounts of HER3 (Fig. 2). Schwann cells also express quantitatively more HER2 than do cells in the oligodendrocyte lineage. Schwann cells express only trace amounts of HER4 (Fig. 2). Similar experiments in both mouse and rat have shown expression of HER2 and HER3 by Schwann cells (24, 34, 45, 46).


Axonal neuregulin signals cells of the oligodendrocyte lineage through activation of HER4 and Schwann cells through HER2 and HER3.

Vartanian T, Goodearl A, Viehöver A, Fischbach G - J. Cell Biol. (1997)

Distinct neuregulin receptor expression by CNS and  PNS glial cells. Primary cultures of astrocytes, O2A progenitor cells,  oligodendrocytes, and Schwann cells were prepared as described.  Cell lysates containing 10 μg of protein were resolved on 4–15%  gradient polyacrylamide gels and probed with HER2, HER3, or  HER4 antibodies. Cells in the oligodendrocyte lineage express  HER2 and HER4, Schwann cells express HER2 and HER3, and  astrocytes express HER2, HER3, and HER4.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139859&req=5

Figure 2: Distinct neuregulin receptor expression by CNS and PNS glial cells. Primary cultures of astrocytes, O2A progenitor cells, oligodendrocytes, and Schwann cells were prepared as described. Cell lysates containing 10 μg of protein were resolved on 4–15% gradient polyacrylamide gels and probed with HER2, HER3, or HER4 antibodies. Cells in the oligodendrocyte lineage express HER2 and HER4, Schwann cells express HER2 and HER3, and astrocytes express HER2, HER3, and HER4.
Mentions: Western blot analysis confirmed the presence of significant levels of HER2 and HER4 and the absence of HER3 in total lysates of cultured O2A progenitor cells and oligodendrocytes (Fig. 2). In contrast to cells in the oligodendrocyte lineage, astrocytes express all three neuregulin receptors (Fig. 2). Unlike cells in the oligodendrocyte lineage, Schwann cells express large amounts of HER3 (Fig. 2). Schwann cells also express quantitatively more HER2 than do cells in the oligodendrocyte lineage. Schwann cells express only trace amounts of HER4 (Fig. 2). Similar experiments in both mouse and rat have shown expression of HER2 and HER3 by Schwann cells (24, 34, 45, 46).

Bottom Line: We have found that oligodendrocite-type II astrocyte (O2A) progenitor cells and mature oligodendrocytes express HER2 and HER4 but no HER3.Coimmunoprecipitation experiments indicate that receptor activation in Schwann cells results in the formation of HER2:HER3 heterodimers.The use of unique neuregulin receptor combinations in oligodendrocytes and Schwann cells likely results in recruitment of different signaling pathways and thus provides a basis for different biological responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.

ABSTRACT
We are interested in the signaling between axons and glia that leads to myelination and maintenance of the myelin internode, and we have focused on the role of neuregulins and their receptors. Neuregulins are a family of ligands that includes heregulin, neu differentiation factor, glial growth factor, and the acetylcholine receptor-inducing activity. Three signal transducing transmembrane receptors for neuregulins, which bear significant homology to the EGF receptor, are currently known: HER2 (erbB2), HER3 (erbB3), and HER4 (erbB4). We have found that oligodendrocite-type II astrocyte (O2A) progenitor cells and mature oligodendrocytes express HER2 and HER4 but no HER3. Schwann cells express HER2 and HER3 but little HER4. In O2A progenitor cells and oligodendrocytes, recombinant neuregulin induces the rapid tyrosine phosphorylation of only HER4. HER2 is not phosphorylated in cells of the oligodendrocyte lineage, but a physical interaction between HER2 and HER4 was detected in coimmunoprecipitation experiments. In Schwann cells, neuregulin induces the phosphorylation of both HER2 and HER3. Coimmunoprecipitation experiments indicate that receptor activation in Schwann cells results in the formation of HER2:HER3 heterodimers. Neuregulin localized immunocytochemically was present on neurites of cultured dorsal root ganglion neurons, and it was released into the medium in a form that promoted receptor tyrosine phosphorylation. Neuregulins therefore meet important criteria expected of molecules involved in axonal-glial signaling. The use of unique neuregulin receptor combinations in oligodendrocytes and Schwann cells likely results in recruitment of different signaling pathways and thus provides a basis for different biological responses.

Show MeSH