Localization of neuregulin isoforms and erbB receptors in myelinating glial cells

Publisher Website
Google Scholar
Abstract
Neuregulins (NRGs) are growth factors present in neurons and glial cells of the central and peripheral nervous systems and play a role in the survival, proliferation, and differentiation of these cells. We now report the localization of the two major isoforms of NRG (α and β) and their receptors (erbB) in cultured Schwann cells and oligodendrocytes isolated from neonatal rat pups. Immunocytochemistry and Western blots for NRG and erbB receptors in defined subcellular fractions were utilized to assess cellular localization. Less differentiated oligodendrocytes contain both NRG isoforms in the cell bodies but not the processes, while only NRG-1β was found in the nucleus. In contrast, more differentiated oligodendrocytes contained neither isoform in the nucleus while both isoforms were colocalized in the cytoplasm and cell processes. In Schwann cells, both NRG-1β and NRG-1α were colocalized in the cytoplasm and processes. The Schwann cell nucleus had weak immunoreactivity for both NRG-1 isoforms, although NRG-1β was predominant. ErbB2 and erbB3 receptors, which transduce the NRG-1 signal in Schwann cells, were found throughout the cytoplasm and in the processes and were also localized in the cell nucleus. The nuclear localization of NRG-1 isoforms and/or erbB receptors in both cell types was confirmed by Western blotting of nuclear and cytoplasmic extracts. Stimulation of Schwann cells with mitotic agents increased NRG-1β expression in the nucleus and dramatically suppressed NRG-1α expression throughout the cell. The functional implications of this differential localization in myelinating cells are discussed.