Activation of Rho GTPases in Smith-Lemli-Opitz syndrome: pathophysiological and clinical implications.

ABSTRACT: Smith-Lemli-Opitz syndrome (SLOS) is a malformation syndrome with neurocognitive deficits due to mutations of DHCR7 that impair the reduction of 7-dehydrocholesterol to cholesterol. To investigate the pathological processes underlying the neurocognitive deficits, we compared protein expression in Dhcr7(+/+) and Dhcr7(Delta3-5/Delta3-5) brain tissue. One of the proteins identified was cofilin-1, an actin depolymerizing factor which regulates neuronal dendrite and axon formation. Differential expression of cofilin-1 was due to increased phosphorylation. Phosphorylation of cofilin-1 is regulated by Rho GTPases through Rho-Rock-Limk-Cofilin-1 and Rac/Cdc42-Pak-Limk-Cofilin-1 pathways. Pull-down assays were used to demonstrate increased activation of RhoA, Rac1 and Cdc42 in Dhcr7(Delta3-5/Delta

SUBMITTER: Jiang XS 

PROVIDER: S-EPMC2838542 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature