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Updated: Aug 26, 2026

Brain Slice Biotinylation: An Ex Vivo Approach to Measure Region-specific Plasma Membrane Protein Trafficking in Adult Neurons
Published on: April 3, 2014
Structural insights enable drug discovery for the neuronal NBCn2 carbonate transporter
Shifan Yang1,2,3, Yihan Zhao1,2,3,4, Sezen Vatansever1,2,3
1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.
Abstract:
NBCn2 (SLC4A10), a member of the SLC4 solute carrier (SLC) family, is a sodium-dependent (bi)carbonate transporter that regulates acid extrusion in various brain regions. Mutations in NBCn2 cause severe neurodevelopmental disorders in humans, and knock out studies suggest that its role in regulating neuronal excitability could hold therapeutic potential for seizure disorders such as epilepsy. Despite its physiological importance, NBCn2's molecular mechanisms remain largely unknown, and there is limited availability of tool compounds to further probe its role in health and disease. Combining cryoEM with computational docking and simulation studies, we herein elucidate NBCn2's molecular architecture and substrate binding mechanisms on the atomic scale. Via structure-based drug discovery we further identify a compound series that inhibits NBCn2-mediated transport, and characterize its inhibitory mechanisms via cryoEM. Lastly, we showcase the potential of this compound series to template useful probes by demonstrating pharmacological activity both in primary culture as well as brain slices.
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