Figure 2.

Model of sortilin function in trafficking of neurotrophins and Trk receptors. Sortilin (gray bar) functions as a coreceptor for the p75NTR receptor (blue) in proneurotrophin signaling pathways. In addition to a role in proneurotrophin signaling, sortilin functions as a trafficking receptor for both Trk receptors and BDNF through the secretory pathway. In BDNF trafficking, the soluble sortilin ectodomain, cleaved of its intracellular sorting signals in the cytoplasmic tail (not membrane associated), rescues BDNF from lysosomal degradation pathways and redirects BDNF through the secretory pathways. Holo sortilin, however, has been demonstrated to mediate BDNF endocytosis and targeting to the lysosome for degradation. Another ligand, progranulin (orange), is targeted to the endosomal-lysosomal pathway through a sortilin-dependent mechanism.