Hypothesized structure of the PIKfyve-ArPIKfyve-Sac3 core complex that generates and cleaves PtdIns3,5P2. This phosphoinositide is a rare and very short lived second messenger whose effector proteins are still largely unknown. Disrupting the physiology of PtdIns3,5P2 metabolism severe disrupts endosome trafficking. Mutations in FIG4, the phosphatase within this complex, result in Yunis-Varon syndrome, a skeletal malformation syndrome with severe neurological impairment, and in Charcot-Marie-Tooth disease type 4J. In their recent publication, Baulac and collaborators identify recessive mutations in FIG4 in a Moroccan family with polymicrogyria and epilepsy. (Figure adapted from http://www.biochemj.org/csb/002/csb002.pdf)
Child Neurology Fellow and epilepsy genetics researcher at the Children’s Hospital of Philadelphia (CHOP), USA and Department of Neuropediatrics, Kiel, Germany
