Neep21 as an effector of the NGF-TrkA signaling endosome

Nerve growth factor (NGF) is a neurotrophin released by peripheral organs during development. NGF binds to and signals through its high-affinity receptor, TrkA, which is expressed by sympathetic neurons in the peripheral nervous system. NGF and TrkA are endocytosed into a signaling endosome in the distal axon of a sympathetic neuron upon peripheral organ innervation and trafficked back to the soma. The survival of sympathetic neurons is dependent on NGF-TrkA signaling. While much is known about the NGF-TrkA signaling endosome in the distal axon, little is known about the action of the signaling endosome upon reaching the soma. Recently, a novel trafficking pathway, signaling transcytosis, was identified as a somatic trafficking route for the NGF-TrkA signaling endosome. Signaling transcytosis is a pathway through which signaling endosomes trafficked to the soma from the growth cone are exocytosed onto the soma membrane and re-endocytosed. Little is known about the effectors of the signaling transcytosis pathway. We have identified a novel effector of the signaling endosome, NEEP21, and have found that it affects the trafficking pathway of the signaling endosome upon arrival in the soma. Neuron enriched endosomal protein of 21kD (NEEP21) is a single pass transmembrane endosomal protein that has been shown to play a role in recycling mechanisms in the somatodendritic region of neurons in the central nervous system. We investigated the role of NEEP21 on NGF-TrkA signaling endosomes in the peripheral nervous system, and found that Neep21 associates with the signaling endosome both before and after signaling transcytosis has occurred. Additionally, although NEEP21 does not affect the number of NGF-TrkA signaling endosomes, it does affect the trafficking route with more signaling endosomes undergoing signaling transcytosis.