Figure 9. NHE6/TrkB signaling endosome pathway model.

(A) NHE6/TrkB signaling endosome in a wild-type neuron. Left. Schema of an endosome. Acidification is regulated by the vacuolar-type H⁺-ATPase (V-ATPase) which pumps protons into the endosome lumen, and NHE6 which allows for proton exit via exchange with Na⁺. On the right, TrkB endosome signaling (radio-waves) is depicted. With binding of BDNF, TrkB is endocytosed and signals from within endosomes. Endosomes are either recycled or traffic through a series of increasingly acidic endosomal compartments leading to degradation in the lysosome. This signaling process contributes substantially to promoting arborization in developing neurons. (B) Depiction of NHE6/TrkB signaling endosome in the NHE6 null neuron. Left. Without NHE6 proton exit from the endosome is impeded resulting in accelerated acidification of the endosome. On the right, upon BDNF binding and endocytosis, the endosomal lumen has accelerated acidification which results in increased degradation of TrkB and attenuated TrkB signaling which leads to an impoverishment of axonal and dendritic arbors.