Neuronal Mislocalization of Mutant DHHC9 in X-Linked Intellectual DIsability
Poster Feb 15, 2017
Lisa Kirouac, Krishna Reddy, Monic Amin and Robert Deschenes
DHHC9 belongs to a family of protein acyl transferase (PAT) enzymes. PATs enzymatically add fatty acid palmitate to cysteine residues on specific protein substrates resulting in increased hydrophobicity and membrane association. This modification is reversible by the action of depalmitoylating thioesterases. There are over 300 candidate palmitoylated proteins identified in rat cortical neurons, suggesting that this dynamic process plays a key role in the spatiotemporal distribution of proteins within the neuron. Neurons are polarized cells with discrete protein domains and DHHC9 and other PATs facilitate proper trafficking of proteins to these domains. Recently, mutations in the zDHHC9 gene have been identified in individuals with X-Linked Intellectual Disability (XLID). Here, we characterize a specific XLID nonsense mutation (*R298) in the zDHHC9 gene that results in the expression of a C-terminal truncated protein, in the context of the mature hippocampal neuron.
Early life stress (ELS) is highly associated with development of psychopathology
and mood disorders in adulthood. Genetic studies have identified variation in the gene calcium voltage-gated channel subunit alpha1C (CACNA1C) to increase risk for several psychiatric disorders. This poster assessed the expression of Cacna1c following prepubertal stress.
We found a distinct subpopulation of Tregs within BMSCs. Tregs and BMSCs in co-culture conferred neuroprotection that varied in a dose-dependent manner. Tregs minimized stem cell production of IL-6, a pro-inflammatory cytokine, and inhibited BMSC secretion of FGF-beta, a cytokine related to BMSC proliferation and differentiation. The ratio of Tregs found natively in BMSCs is optimally adapted to provide the maximum neuroprotective benefit of stem cell treatment after ischemic stroke.READ MORE