Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4.
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.
Stendel
Claudia
C
Institute of Cell Biology, ETH Zürich, Schafmattstrasse 18, CH-8093 Zürich, Switzerland. claudia.stendel@cell.biol.ethz.ch
Roos
Andreas
A
Deconinck
Tine
T
Pereira
Jorge
J
Castagner
Francois
F
Niemann
Axel
A
Kirschner
Janbernd
J
Korinthenberg
Rudolf
R
Ketelsen
Uwe-Peter
UP
Battaloglu
Esra
E
Parman
Yesim
Y
Nicholson
Garth
G
Ouvrier
Robert
R
Seeger
Jürgen
J
De Jonghe
Peter
P
Weis
Joachim
J
Krüttgen
Alexander
A
Rudnik-Schöneborn
Sabine
S
Bergmann
Carsten
C
Suter
Ueli
U
Zerres
Klaus
K
Timmerman
Vincent
V
Relvas
João B
JB
Senderek
Jan
J
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*
C485164:FGD4 protein, human; D008840:Microfilament Proteins; D020741:rho GTP-Binding Proteins