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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adolescent
-
Adult
-
Amino Acid Sequence
-
Charcot-Marie-Tooth Disease / genetics*
-
Charcot-Marie-Tooth Disease / pathology
-
Child
-
Demyelinating Diseases / genetics*
-
Demyelinating Diseases / pathology
-
Female
-
Humans
-
Male
-
Microfilament Proteins / analysis
-
Microfilament Proteins / genetics*
-
Molecular Sequence Data
-
Mutation
-
Myelin Sheath / enzymology*
-
Myelin Sheath / pathology
-
Peripheral Nerves / enzymology*
-
Peripheral Nerves / pathology
-
Schwann Cells / enzymology
-
Schwann Cells / pathology
-
rho GTP-Binding Proteins / analysis
-
rho GTP-Binding Proteins / genetics*
Substances
-
FGD4 protein, human
-
Microfilament Proteins
-
rho GTP-Binding Proteins
Associated data
-
RefSeq/NM_139232
-
RefSeq/NM_139241