California Institute of Technology (CalTech)

Ion Channel Assembly in Neuronal Degeneration

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The brain is a critical organ whose function relies on the billions of neurons that it contains. To communicate, neurons need to be able to detect and propagate signals to neighboring cells. These signals can be stored as intracellular ion concentrations, which are generated by the action of ion channels in the synaptic plasma membrane. Functional ion channels are therefore vital to proper brain function: problems can cause severe physiological effects in humans, and different classes of ion channels have been implicated in neurodegenerative conditions including Alzheimer’s, Parkinson’s and Huntington’s disease.

Ion channels are made up of multiple subunits that must be assembled into an oligomeric complex to be functional. This is a major challenge for the cell: subunits must be made and inserted into the membrane of the endoplasmic reticulum individually, then must come together with the correct arrangement and stoichiometry, and finally any orphan subunits must be recognized and degraded. Despite the critical nature of this process, we have little understanding of how this process is facilitated and regulated. My data has begun to address some of these underlying questions, and has opened up new pathways to understand these fundamental mechanisms.