Prof Peter Brophy
The lab focuses on the assembly of the node of Ranvier in response to myelination and the function of Schwann cells in the peripheral nervous system.
Peter Brophy received his BSc from King's College, London University and PhD from Guy's Hospital Medical School (now King's College Medical School), London University. He was the Chair of Veterinary Anatomy & Cell Biology in the Vet School from 1995 to 2009 and Chair of Anatomy in the Medical School from 2009 to 2014 and was the Director of the Centre for Neuroregeneration (formerly the Centre for Neuroscience Research) from 2002 to 2014.
He has served on the research panels of a variety of bodies including the UK Multiple Sclerosis Society and the Neurosciences Panel of the Wellcome Trust. He has Chaired the International Gordon Conference on Myelin and currently Chairs the Scientific Advisory Board of the Institut du Fer à Moulin, Paris. He is a member of the MRC Training and Career Development Panel and the Neuroscience Committee of the French Agence Nationale de la Recherche.
In the developing vertebrate nervous system oligodendrocytes and Schwann cells not only play a vital role in promoting neuron survival, but they also produce the myelin sheath, which is essential for the normal function of the nervous system, a fact underscored by the debilitating consequences of demyelination in multiple sclerosis in the CNS and in peripheral neuropathies of the Charcot-Marie-Tooth (CMT) type.
The discovery of the Periaxin (Prx) gene and its role in forming the Cajal bands (first described by Santiago Ramon y Cajal) in Schwann cells led to the identification of the cause of a severe demyelinating neuropathy-CMT 4F-in humans. This work also permitted the first experimental proof of the proposal by Huxley and Stämpfli (1949) that internodal distance can regulate nerve conduction velocity.
A second project is focused on the assembly of two structures in the axon that are required for rapid nerve conduction: the axon initial segment (AIS) and the nodes of Ranvier. We have found that three isoforms of neurofascin, one glial, and two neuronal, play distinct but vital roles in the clustering of voltage-gated sodium channels at the node of Ranvier. Neuronal neurofascin also has a vital role at the AIS. Recently we discovered that delivery of this membrane protein to the AIS occurs by a remarkably circuitous route. These studies exploit live imaging using both conventional and super-resolution microscopy.
- Aniket Ghosh, Post-Doctoral Fellow
Malavasi, E.L.V., A. Ghosh, D.G. Booth, M. Zagnoni, D.L. Sherman and P.J. Brophy (2021). Dynamic early clusters of nodal proteins contribute to node of Ranvier assembly during myelination of peripheral neurons. eLife (in press).
Ghosh, A., E.L.V. Malavasi, D.L. Sherman and P.J. Brophy (2020). Neurofascin and Kv7.3 are delivered to somatic and axon terminal surface membranes en route to the axon initial segment. eLife 2020;9:e60619.
Smigiel, R., D.L Sherman, M. Rydzanicz, A. Walczak, D. Mikolajkow, B. Krolak-Olejnik, J. Kosinska, P. Gasperowicz, A. Biernacka, P. Stawinski, M. Marciniak, W. Andrzejewski, M. Boczar, P. Krajewski, M.M. Sasiadek, P.J. Brophy* and R. Ploski* (2018). Homozygous mutation in the Neurofascin gene affecting the glial isoform of Neurofascin causes severe neurodevelopment disorder with hypotonia, amimia and areflexia. Hum. Mol. Genet. 27, 3669-3674 *Joint senior authors
Ghosh, A., D.L. Sherman and P.J. Brophy (2018). The Axonal Cytoskeleton and the Assembly of Nodes of Ranvier. Neuroscientist 24, 104-110.
Brivio, V., C. Faivre-Sarrailh, E.Peles; D.L. Sherman and P.J. Brophy (2017). Assembly of CNS Nodes of Ranvier in Myelinated Nerves is Promoted by the Axon Cytoskeleton. Current Biology 27(7):1068-1073.
- Amor, V., C. Zhang, A. Vainshtein, A. Zhang, D.R. Zollinger, Y. Eshed-Eisenbach, P.J. Brophy, M.N. Rasband, and E. Peles (2017). The paranodal cytoskeleton clusters Na+ channels at nodes of Ranvier, eLife 6
- A. Zhang, A. Desmazières, B. Zonta, S. Melrose, G. Campbell, D. Mahad, Q. Li, D.L. Sherman, R. Reynolds and P.J. Brophy (2015). Neurofascin 140 is an Embryonic Neuronal Neurofascin Isoform that Promotes the Assembly of the Node of Ranvier. J. Neurosci 5: 2246-2254.
- K-J. Chang, D.R. Zollinger, K. Susuki, D.L. Sherman, P.J. Brophy, E.C. Cooper, V. Bennett, P.J. Mohler and M.N. Rasband (2014). Glial Ankyrins Facilitate Paranodal Axoglial Junction Assembly in the Central Nervous System. Nature Neuroscience 17: 1673-1681.
- A. Desmazières, B. Zonta, A. Zhang, L.M.N. Wu, D.L. Sherman and P.J. Brophy (2014). Differential Stability of PNS and CNS Nodal Complexes when Neuronal Neurofascin is Lost. J. Neurosci 4: 5083-5088 (Cover).
Key Earlier Publications
- L.M.N. Wu, A. Williams, A. Delaney, D.L. Sherman and P.J. Brophy (2012). Increasing Internodal Distance in Myelinated Nerves Accelerates Nerve Conduction to a Flat Maximum. Current Biology 22: 1957-1961.
- B. Zonta, A. Desmazieres, A. Rinaldi, S. Tait, D.L. Sherman, M.F. Nolan and PJ Brophy (2011). A Critical Role for Neurofascin in Regulating Action Potential Initiation Through Maintenance of the Axon Initial Segment. Neuron 69, 945-956.
- B. Zonta, S. Tait, S. Melrose, H. Anderson, S. Harroch, J. Higginson, D.L. Sherman and P.J. Brophy (2008). Glial and Neuronal Isoforms of Neurofascin have Distinct Roles in the Assembly of Nodes of Ranvier in the Central Nervous System. J. Cell Biol 181: 1169-1177.
- D.L. Sherman, S. Tait, S. Melrose, R. Johnson, B.Zonta, F.A. Court, W.B. Macklin, S. Meek, A.J. Smith, D.F. Cottrell and PJ Brophy (2005). Organization of Axonal Domains for Saltatory Conduction Requires the Neurofascins. Neuron 48: 737-742 (Cover).
- F.A. Court, D.L. Sherman, T. Pratt, E.M. Garry, R.R. Ribchester, D.F. Cottrell, S.M. Fleetwood-Walker and PJ Brophy (2004). Restricted Growth of Schwann Cells Lacking Cajal Bands Slows Conduction in Myelinated Nerves. Nature 431, 191-195 (Cover).