Seminars

Modulation of ion channel expression, localization and function by diverse molecular mechanisms underlies plasticity in neurotransmission.  My laboratory is particularly interested in dynamic regulation of voltage-sensitive ion channel abundance, localization and function through reversible protein phosphorylation. We have identified a number of neuronal ion channels that are regulated through phosphorylation, and have investigated mechanisms underlying this regulation.  We have used mass spectrometric based proteomics approaches to identify the in vivo phosphorylation sites on ion channels purified from brain, and used mutagenesis to identify the roles of phosphorylation at specific sites in the modulation of specific aspects of ion channel abundance, localization and function in response to physiological and pathological stimuli.  We have also used phosphospecific antibodies to study regulation at specific sites in more detail, including the specific protein kinase and phosphatase systems that mediate changes in phosphorylation state.  Recent studies have focused on methylation as a novel modification to voltage-gated ion channels, and its reciprocal regulation relative to phosphorylation. These studies have provided new insights into the nature and extent of how dynamic changes in posttranslational modification of ion channels contribute to plasticity of signaling in mammalian neurons.   See Misonou et al., 2006: Cerda & Trimmer, 2011.