Lowe syndrome: Between primary cilia assembly and Rac1-mediated membrane remodeling
- Authors
- Madhivanan, K., Mukherjee, D., and Aguilar, R.C.
- ID
- ZDB-PUB-130709-14
- Date
- 2012
- Source
- Communicative & integrative biology 5(6): 641-644 (Journal)
- Registered Authors
- Keywords
- primary cilia, cell spreading, cell migration, Rac1 and RhoA signaling
- MeSH Terms
- none
- PubMed
- 23739214 Full text @ Commun. Integr. Biol.
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.