Affiliations: 1) University of Montana, Missoula, MT; 2) Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, MT
Keywords: f. neuromuscular junction; j. ion channels
Emerging evidence points to a link between pH imbalances, and psychiatric conditions such as schizophrenia, autism spectrum disorder, and bipolar disorder. Due to its wide-ranging potential for new treatment approaches, it is imperative to establish whether altered pH may influence neural development and drive disease pathology. Intracellular pHcan influence critical developmental pathways including cell migration, ion channel activity and abundance, and protein trafficking. However, it’s not clear which of these processes act as pH-dependent modifiers of neuronal development. Na+/H+ exchangers (Nhe) are major regulators of pH and electrolyte balance, essential for brain development and neural function. Disruption of Nhes in early life is associated with developmental disorders including microcephaly, intellectual disabilities, autism, and febrile seizures, but the specific role of Nhes in disease manifestation is not well understood. Compared to mammalian genomes which typically encode 9 Nhe proteins, Drosophila melanogaster encodes 3, making them a more straightforward model to elucidate Nhe function. Development of the Drosophila neuromuscular junction (NMJ) is an activity-dependent process, which precisely controls the number of synaptic boutons. It is known that pH-sensitive, presynaptic ion channels play a role in regulating neuronal excitability and bouton number at the NMJ. In addition, transient changes in pH at the synaptic cleft have been observed following an action potential, but how pH influences neuronal development and morphology is unclear. We find that altered Nhe2 expression affects bouton number at the NMJ. This work defines a new role for Nhe proteins in neuronal morphology and development.