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Peter J. Brophy"How vertebrate nerves switch to saltatory conduction"

Abstract :


A distinguishing feature of complex nervous systems is their ability to transmit nerve impulses rapidly by saltatory conduction.
The primary goals of our research are first to understand how the myelin sheath is assembled around nerve fibres, and secondly to reveal the molecular mechanisms by which myelination induces the establishment of the axonal domains that are essential for rapid nerve impulse conduction.
We have described a new dystroglycan receptor complex in the Schwann cell plasma membrane that has an essential function in mouse and man. Remarkably, this complex accurately delineates the “longitudinal bands” first described by the great Spanish neuroanatomist Santiago Ramon y Cajal in the late 19th century. We have named these longitudinal cytoplasmic structures in Schwann cells Cajal bands to acknowledge both Ramón y Cajal’s discovery and our growing understanding of their function. Secondly, we have identified two essential pioneer proteins that nucleate the assembly of the node of Ranvier in vertebrate nerves. These proteins are glial and neuronal isoforms of the cell adhesion molecule Neurofascin respectively. Surprisingly these proteins have quite distinct roles in the establishment of nodes in the CNS versus the PNS.

Selected publications

Szigeti K, Wiszniewski W, Saifi GM, Sherman DL, Sule N, Adesina AM, Mancias P, Papasozomenos SCh, Miller G, Keppen L, Daentl D, Brophy PJ, Lupski JR.
Functional, histopathologic and natural history study of neuropathy associated with EGR2 mutations.
Neurogenetics. 2007 Nov;8(4):257-62. Epub 2007 Aug 24.
Grove M, NH Komiyama, K-A Nave, Seth G Grant, DL Sherman and PJ Brophy (2007). FAK is required for axonal sorting by Schwann cells. J Cell Biol 176: 277-282.
Sherman DL, S Tait, S Melrose, R Johnson, B Zonta, FA Court, WB Macklin, S Meek, AJ Smith, DF Cottrell, and PJ Brophy (2005). Organization of axonal domains for saltatory conduction requires the neurofascins. Neuron 48: 737-742 (Cover) .
Court F A, DL Sherman, T Pratt, EM Garry, RR Ribchester, DF Cottrell, SM Fleetwood-Walker, and PJ Brophy (2004). Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves. Nature 431: 191-195 (Cover).

Stéphane Oliet