Stendel Claudia, Roos Andreas, Deconinck Tine, Pereira Jorge, Castagner Francois, Niemann Axel, Kirschner Janbernd, Korinthenberg Rudolf, Ketelsen Uwe-Peter, Battaloglu Esra, Parman Yesim, Nicholson Garth, Ouvrier Robert, Seeger Jürgen, De Jonghe Peter, Weis Joachim, Krüttgen Alexander, Rudnik-Schöneborn Sabine, Bergmann Carsten, Suter Ueli, Zerres Klaus, Timmerman Vincent, Relvas João B, Senderek Jan
Institute of Cell Biology, ETH Zürich, Schafmattstrasse 18, CH-8093 Zürich, Switzerland.
Am J Hum Genet. 2007 Jul;81(1):158-64. doi: 10.1086/518770. Epub 2007 May 24.
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.
Rho亚家族的GTP酶广泛参与脊椎动物神经系统的髓鞘形成。Rho GTP酶活性受到一组特定鸟嘌呤核苷酸交换因子（GEFs）的时空调节。在此，我们报告，frabin/FGD4（一种Rho GTP酶细胞分裂周期42（Cdc42）的GEF）的破坏会导致常染色体隐性遗传性夏科-马里-图斯（CMT）神经病患者出现周围神经脱髓鞘。这些数据，连同frabin在转染的施万细胞中诱导Cdc42介导的细胞形态变化的能力，表明Rho GTP酶信号传导对于周围神经系统的正常髓鞘形成至关重要。
