Patients with fragile X syndrome have a higher susceptibility to epilepsy, but the exact mechanisms are unknown. Our previous work suggested a potential molecular mechanism by showing that FMRP controls the mRNA translation and cell surface expression of the A-type potassium channel Kv4.2, a major regulator of neuronal excitability in the hippocampus (Gross et al., 2011). The lab is currently following up on these findings by investigating how FMRP and microRNAs regulate Kv4.2 expression during epilepsy. 

Proposed Model of Kv4.2 regulation: Expression levels of Kv4.2 in neurons are tightly controlled by FMRP and microRNAs that antagonize each other in regulating Kv4.2 mRNA translation. Increased Kv4.2 mRNA translation may counteract endocytosis of Kv4.2 induced by external stimuli. We hypothesize that defects in the regulation of Kv4.2 mRNA translation may contribute to epileptic seizures and epileptogenesis. 

PI3K enzymatic activity is mediated by p110 catalytic subunits. There are four class 1 PI3K catalytic subunits, p110a, p110β, p110γ and p110δ, and recent research has shown that these subunits are not functionally redundant, but have specific roles downstream of distinct neuronal receptor signaling complexes. Moreover, the p110 subunits have been implicated in a subset of different neuronal diseases, including autism, epilepsy and schizophrenia. One focus of the Gross Lab is to understand the differential regulation and signaling of these catalytic subunits in neurons and how their dysfunction leads to disease.

Taken from Gross C and Bassell GJ (2014) Front. Mol. Neurosci. 7:12. doi: 10.3389/fnmol.2014.00012.