Trafficking of Heparanase 1 is regulated by neuronal activity during homeostatic synaptic plasticity

Abstract

Activity regulated protein trafficking in neurons comprises an important mechanism of synaptic plasticity. In this study, we found the lysosomal enzyme heparanase 1 (HPA1) which cleaves heparan sulfate (HS) moiety undergoes axonal and dendritic trafficking in an activity-dependent manner. Persistent increase of neuronal activity permitting the induction of homeostatic weakening of synaptic transmission leads to an elevation of synaptic accumulation of the enzyme despite of no overall expression change. Knock down of HPA1 significantly reduces excitatory synaptic density in vitro and abolishes the induction of normal homeostatic synaptic scaling down. The regulatory role of HPA1 in synaptic plasticity could be achieved by enzymatic modification of synaptic HS. Our study reveals a previously undefined role of the mammalian endoglycosidase HPA1 in nervous system and also highlights the importance of extracellular matrix modification for induction of homeostatic synaptic plasticity.