title: Lowe syndrome: Between primary cilia assembly and Rac1-mediated membrane remodeling.
abstract: Lowe syndrome (LS) is a lethal X-linked genetic disease caused by functional deficiencies of the phosphatidlyinositol 5-phosphatase, Ocrl1. In the past four years, our lab described the first Ocrl1-specific cellular phenotypes using dermal fibroblasts from LS patients. These phenotypes, validated in an ocrl1-morphant zebrafish model, included membrane remodeling (cell migration/spreading, fluid-phase uptake) defects and primary cilia assembly abnormalities. On one hand, our findings unraveled cellular phenotypes likely to be involved in the observed developmental defects; on the other hand, these discoveries established LS as a ciliopathy-associated disease. This article discusses the possible mechanisms by which loss of Ocrl1 function may affect RhoGTPase signaling pathways leading to actin cytoskeleton rearrangements that underlie the observed cellular phenotypes.
authors.affiliation: Department of Biological Sciences; Purdue University; West Lafayette, IN USA.
authors.forename: Kayalvizhi
authors.initials: K
authors.lastname: Madhivanan
authors.forename: Debarati
authors.initials: D
authors.lastname: Mukherjee
authors.forename: R Claudio
authors.initials: RC
authors.lastname: Aguilar
keywords: Rac1 and RhoA signaling; cell migration; cell spreading; primary cilia