Axon terminals control endolysosome diffusion to support synaptic remodelling

Abstract

Endolysosomes are acidic organelles formed by the fusion ofendosomes with lysosomes. In the presynaptic compartment theycontribute to protein homeostasis, the maintenance of vesiclepools and synaptic stability. Here, we evaluated the mobility ofendolysosomes found in axon terminals of olfactory sensoryneurons ofXenopus tropicalistadpoles. F-actin restricts themotion of these presynaptic acidic organelles which is characterized by a diffusion coefficient of 6.7 × 1023μm2⋅s21. Local injection of secreted protein acidic and rich in cysteine (SPARC) inthe glomerular layer of the olfactory bulb disrupts the structureof synaptic F-actin patches and increases the presence andmobility of endolysosomal organelles found in axon terminals.The increased motion of endolysosomes is localized to the presynaptic compartment and does not promote their access toaxonal regions for retrograde transportation to the cell body. Local activation of synaptic degradation mechanisms mediated by SPARC coincides with a loss of the ability of tadpoles to detect waterborne odorants. Together, these observations show that the diffusion of presynaptic endolysosomes increases during conditions of synaptic remodelling to support their local degradativeactivity.