GPRIN1 modulates neuronal signal transduction and affects mouse-learning behavior

ABSTRACT In the adult and developing brain, G protein-regulated inducer of neurite outgrowth 1 (GPRIN1) is a downstream effector for Gα o/i/z proteins that promotes neurite outgrowth. However, so far, the physiological role of GPRIN1 in brain health has not been reported. We generated a viable GPRIN1 whole-body knockout mouse to assess its physiological role in synaptic function both ex vivo and in vivo . In adult neurons, GPRIN1 is highly localized to the plasma membrane and synapses where it regulates neuronal signal transduction and Ca 2+ homeostasis. Our results reveal that GPRIN1 might be a novel protein involved in agonist-stimulated cytoskeletal reorganization, which is crucial for early neuronal network development and in functionally mature neurons. Finally, we show that loss of GPRIN1 leads to a learning deficit in vivo and sensitizes neurons to stress, suggesting a modulatory role in brain health and disease.