title: Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4.
abstract: GTPases of the Rho subfamily are widely involved in the myelination of the vertebrate nervous system. Rho GTPase activity is temporally and spatially regulated by a set of specific guanine nucleotide exchange factors (GEFs). Here, we report that disruption of frabin/FGD4, a GEF for the Rho GTPase cell-division cycle 42 (Cdc42), causes peripheral nerve demyelination in patients with autosomal recessive Charcot-Marie-Tooth (CMT) neuropathy. These data, together with the ability of frabin to induce Cdc42-mediated cell-shape changes in transfected Schwann cells, suggest that Rho GTPase signaling is essential for proper myelination of the peripheral nervous system.
authors.affiliation: Institute of Cell Biology, ETH Zürich, Schafmattstrasse 18, CH-8093 Zürich, Switzerland. claudia.stendel@cell.biol.ethz.ch
authors.forename: Claudia
authors.initials: C
authors.lastname: Stendel
authors.forename: Andreas
authors.initials: A
authors.lastname: Roos
authors.forename: Tine
authors.initials: T
authors.lastname: Deconinck
authors.forename: Jorge
authors.initials: J
authors.lastname: Pereira
authors.forename: Francois
authors.initials: F
authors.lastname: Castagner
authors.forename: Axel
authors.initials: A
authors.lastname: Niemann
authors.forename: Janbernd
authors.initials: J
authors.lastname: Kirschner
authors.forename: Rudolf
authors.initials: R
authors.lastname: Korinthenberg
authors.forename: Uwe-Peter
authors.initials: UP
authors.lastname: Ketelsen
authors.forename: Esra
authors.initials: E
authors.lastname: Battaloglu
authors.forename: Yesim
authors.initials: Y
authors.lastname: Parman
authors.forename: Garth
authors.initials: G
authors.lastname: Nicholson
authors.forename: Robert
authors.initials: R
authors.lastname: Ouvrier
authors.forename: Jürgen
authors.initials: J
authors.lastname: Seeger
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Alexander
authors.initials: A
authors.lastname: Krüttgen
authors.forename: Sabine
authors.initials: S
authors.lastname: Rudnik-Schöneborn
authors.forename: Carsten
authors.initials: C
authors.lastname: Bergmann
authors.forename: Ueli
authors.initials: U
authors.lastname: Suter
authors.forename: Klaus
authors.initials: K
authors.lastname: Zerres
authors.forename: Vincent
authors.initials: V
authors.lastname: Timmerman
authors.forename: João B
authors.initials: JB
authors.lastname: Relvas
authors.forename: Jan
authors.initials: J
authors.lastname: Senderek
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology; D002648:Child; D003711:Demyelinating Diseases / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009186:Myelin Sheath / Q000201:enzymology* / Q000473:pathology; D010525:Peripheral Nerves / Q000201:enzymology* / Q000473:pathology; D012583:Schwann Cells / Q000201:enzymology / Q000473:pathology; D020741:rho GTP-Binding Proteins / Q000032:analysis / Q000235:genetics*
chemical_list: C485164:FGD4 protein, human; D008840:Microfilament Proteins; D020741:rho GTP-Binding Proteins