- Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4.
Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4.
American journal of human genetics (2007-06-15)
Claudia Stendel, Andreas Roos, Tine Deconinck, Jorge Pereira, Francois Castagner, Axel Niemann, Janbernd Kirschner, Rudolf Korinthenberg, Uwe-Peter Ketelsen, Esra Battaloglu, Yesim Parman, Garth Nicholson, Robert Ouvrier, Jürgen Seeger, Peter De Jonghe, Joachim Weis, Alexander Krüttgen, Sabine Rudnik-Schöneborn, Carsten Bergmann, Ueli Suter, Klaus Zerres, Vincent Timmerman, João B Relvas, Jan Senderek
PMID17564972
RESUMEN
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.