Rab10 regulates the sorting of internalised TrkB to retrograde axonal transport

Abstract

Neurons process real-time information from axon terminals to coordinate gene expression, growth and plasticity. Input from distal axons is encoded as a stream of endocytic organelles, termed signalling endosomes, targeted to the soma. Formation of these organelles depends on target-derived molecules, such as brain-derived neurotrophic factor (BDNF), which is recognised by TrkB receptors on the plasma membrane, endocytosed and transported to the cell body along the microtubules network. Notwithstanding its neuropathological importance, the mechanism controlling the sorting of TrkB to signalling endosomes is currently unknown. In this work, we uncover the small GTPase Rab10 as critical for TrkB sorting and propagation of BDNF signalling from axon terminals to the soma. Our data demonstrate that Rab10 defines a novel class of axonal organelles, rapidly mobilised towards the axon terminal upon BDNF stimulation, enabling the axon to fine-tune retrograde signalling depending on BDNF availability at the synapse. These results help clarifying the neuroprotective phenotype recently associated to Rab10 polymorphisms and provide a new therapeutic target to halt neurodegeneration.