Affiliations: 1) University of Montana, Missoula MT; 2) Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, MT
Keywords: j. ion channels; q. developmental modulation
Electrolyte balance and the maintenance of physiological pH are important in all cells across the animal kingdom. Sodium (Na+) Proton (H+) Exchangers (Nhe) are powerful proteins with the capacity to shape their cellular environment by acting as major modifiers of electrolyte balance and pH. They have emerged as important regulators of cell size, cellular metabolism, and neural excitability. Despite their potential to influence many key processes in brain development, their role in neurogenesis is not well defined. Human mutations in Nhe proteins are found to cause microcephaly, autism, and epileptic seizures, but how they drive disease pathology is not well understood. Defining the role of Nhe proteins in neurogenesis and disease is complicated by the fact that there are 9 Nhe proteins encoded by the human genome, which influence pH at the cell membrane as well as within intracellular organelles. As flies have only 3 Nhe proteins, we can use this simplified system to define precise defects in proliferation, neural formation and identity that are caused by loss or mutation of Nhe proteins. Our preliminary findings reveal that reduction/loss of Nhe proteins reduces overall brain size and influences proliferation in specific neuroblast lineages. This work will define pH-sensitive cellular processes and signaling pathways regulated by Nhe proteins.