Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4


STENDEL C., ROOS A., DECONINCK T., PEREIRA J., CASTAGNER F., NIEMANN A., ...More

AMERICAN JOURNAL OF HUMAN GENETICS, vol.81, no.1, pp.158-164, 2007 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 81 Issue: 1
  • Publication Date: 2007
  • Doi Number: 10.1086/518770
  • Journal Name: AMERICAN JOURNAL OF HUMAN GENETICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.158-164
  • Istanbul University Affiliated: Yes

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.