Abstract
Homophilic interactions of the major integral membrane protein of peripheral nerve myelin, P0-glycoprotein, are thought to mediate membrane adhesion and compaction. Molecular modeling of its extracellular domain (P0-ED), based on its resemblance to an immunoglobulin variable domain and on X-ray diffraction measurements of inter-membrane spacings of myelin, has suggested which amino acid sidechains may be involved in the homophilic adhesion. Recently identified point-mutations in the human P0 gene result in amino acid substitutions in P0 protein and correlate with demyelinating motor and sensory neuropathies. The molecular model explains how these changes result in disrupted P0-P0 interactions; indicates how compensatory changes in amino acids, as occur in P0-ED of other species, preserve normal homophilic interactions; and predicts what other residue substitutions might underlie additional cases of demyelinating neuropathies.
References
Jan 1, 1992·Journal of Molecular Neuroscience : MN·J KarthigasanD A Kirschner
Nov 13, 1992·Cell·K P GieseM Schachner
Mar 1, 1990·Neuron·D D'UrsoD R Colman
Jan 1, 1990·Journal of Neuroscience Research·M Barbu
Apr 26, 1990·Nature·M T FilbinG I Tennekoon
Oct 31, 1991·Biochemical and Biophysical Research Communications·K HayasakaK Uyemura
Jun 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·C LaiJ G Sutcliffe
Aug 1, 1989·Journal of Molecular Evolution·R A SaavedraL Hood
Mar 1, 1988·Neuron·G LemkeJ Patterson
Feb 1, 1988·Biophysical Journal·H Inouye, D A Kirschner
Jan 1, 1974·Clinical Genetics·H Skre
Jan 10, 1980·Nature·D A Kirschner, A L Ganser
Dec 1, 1993·Journal of Neurochemistry·C A WellsD A Kirschner
Nov 1, 1993·Nature Genetics·K HayasakaN Tachi
Aug 16, 1993·Biochemical and Biophysical Research Communications·K HayasakaY Murai
Sep 1, 1993·Nature Genetics·K HayasakaP F Chance
Sep 1, 1993·Nature Genetics·T KulkensJ E Hoogendijk
Sep 1, 1993·Human Molecular Genetics·K HayasakaV V Ionasescu
Nov 1, 1993·Nature Genetics·B B RoaJ R Lupski
Jul 8, 1993·The New England Journal of Medicine·B B RoaJ R Lupski
Jan 1, 1987·Immunology Today·A F Williams
Citations
Nov 15, 1996·Journal of Neuroscience Research·D A KirschnerP A Bolhuis
Apr 1, 1997·Annals of Neurology·T D BirdS M Sumi
Feb 6, 1998·Human Mutation·E Sorour, M Upadhyaya
Dec 3, 1999·Journal of the Neurological Sciences·A OhnishiM Ikeda
Nov 2, 1999·Neuromuscular Disorders : NMD·A LaguenyA Vandenberghe
Jan 7, 1998·Journal of Anatomy·R Martini
Oct 13, 2010·The Journal of Biological Chemistry·Robin L AvilaDaniel A Kirschner
Jun 30, 2007·Annual Review of Neuroscience·Lawrence ShapiroDavid R Colman
Jun 1, 1996·Neurochemical Research·L M SuneethaA S Balasubramanian
Jan 1, 1998·Drug Delivery·M FoldvariC Mezei
Nov 15, 1996·Structure·D A KirschnerR A Saavedra
Oct 1, 1996·Annals of Neurology·P H MeijerinkP A Bolhuis
Nov 1, 1995·Nature Genetics·R MartiniM Schachner
Dec 5, 2006·Muscle & Nerve·Paraskewi FloroskufiDemetris Vassilopoulos
Jan 1, 1996·Human Mutation·I SahlyJ L Dufier
Jul 22, 1998·Microscopy Research and Technique·R Martini, S Carenini
Jan 1, 1996·Human Mutation·E BelloneF Ajmar
Oct 6, 2007·Biochemistry·Megan L PlotkowskiJames U Bowie