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PLoS Biology Issue Image | Vol. 15(6) June 2017

Laminin 211 inhibits protein kinase A in Schwann cells to modulate neuregulin 1 type III-driven myelination

Myelin is formed by the wrapping of glial cell membranes around axons and is required for the fast conduction of nerve impulses and to support axons. In the peripheral nervous system, myelin is produced by Schwann cells, and defects in peripheral myelin can cause debilitating diseases whose molecular mechanisms are only partially understood. This study by Ghidinelli et al. reveals how two crucial extracellular modulators of myelin formation—neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211)—work together in the peripheral nervous system. Although Lm211 was believed to promote myelination, the authors show here that it can also inhibit myelin formation by suppressing the activity of Nrg1III, limiting the activation of its downstream signaling cascade. These results help to explain why certain inherited neuropathies are characterized by hypermyelination and redundant myelin sheaths. The image shows myelin formed in vitro by Schwann cells when co-cultured with dorsal root ganglion neurons for this study.

Image Credit: Angelo Quattrini and Paola Podini, San Raffaele Scientific Institute

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Laminin 211 inhibits protein kinase A in Schwann cells to modulate neuregulin 1 type III-driven myelination

Myelin is formed by the wrapping of glial cell membranes around axons and is required for the fast conduction of nerve impulses and to support axons. In the peripheral nervous system, myelin is produced by Schwann cells, and defects in peripheral myelin can cause debilitating diseases whose molecular mechanisms are only partially understood. This study by Ghidinelli et al. reveals how two crucial extracellular modulators of myelin formation—neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211)—work together in the peripheral nervous system. Although Lm211 was believed to promote myelination, the authors show here that it can also inhibit myelin formation by suppressing the activity of Nrg1III, limiting the activation of its downstream signaling cascade. These results help to explain why certain inherited neuropathies are characterized by hypermyelination and redundant myelin sheaths. The image shows myelin formed in vitro by Schwann cells when co-cultured with dorsal root ganglion neurons for this study.

Image Credit: Angelo Quattrini and Paola Podini, San Raffaele Scientific Institute

https://doi.org/10.1371/image.pbio.v15.i06.g001