Tissue plasminogen activator regulates Purkinje neuron development and survival

Cerebellar Purkinje neurons (PNs) strongly affect motor coordination and learning. PN study has contributed significantly to fundamental concepts of modern neuroscience. The present investigation defines distinctive molecular signaling pathways through which tissue plasminogen activator/plasmin-based proteolysis regulates postnatal PN dendrite development, synapse formation, mitochondrial morphology and function, and PN survival. These pathways involve differentially acting downstream constituents, including protein kinase Cγ, brain-derived neurotrophic factor, and a voltage-dependent anion channel. The metabolic mechanisms established here may apply to the development and degeneration of PNs and additional types of neurons in many animal and human brain diseases in which PNs are notably vulnerable.