| First Author | Connor B | Year | 2023 |
| Journal | Proc Natl Acad Sci U S A | Volume | 120 |
| Issue | 6 | Pages | e2205426120 |
| PubMed ID | 36730190 | Mgi Jnum | J:338830 |
| Mgi Id | MGI:7516064 | Doi | 10.1073/pnas.2205426120 |
| Citation | Connor B, et al. (2023) Transcytosis-mediated anterograde transport of TrkA receptors is necessary for sympathetic neuron development and function. Proc Natl Acad Sci U S A 120(6):e2205426120 |
| abstractText | In neurons, many membrane proteins, synthesized in cell bodies, must be efficiently delivered to axons to influence neuronal connectivity, synaptic communication, and repair. Previously, we found that axonal targeting of TrkA neurotrophin receptors in sympathetic neurons occurs via an atypical transport mechanism called transcytosis, which relies on TrkA interactions with PTP1B, a protein tyrosine phosphatase. Here, we generated TrkA(R685A) mice, where TrkA receptor signaling is preserved, but its PTP1B-dependent transcytosis is disrupted to show that this mode of axonal transport is essential for sympathetic neuron development and autonomic function. TrkA(R685A) mice have decreased axonal TrkA levels in vivo, loss of sympathetic neurons, and reduced innervation of targets. The neuron loss and diminished target innervation phenotypes are specifically restricted to the developmental period when sympathetic neurons are known to rely on the TrkA ligand, nerve growth factor, for trophic support. Postnatal TrkA(R685A) mice exhibit reduced pupil size and eyelid ptosis, indicative of sympathetic dysfunction. Furthermore, we also observed a significant loss of TrkA-expressing nociceptive neurons in the dorsal root ganglia during development in TrkA(R685A) mice, suggesting that transcytosis might be a general mechanism for axonal targeting of TrkA receptors. Together, these findings establish the necessity of transcytosis in supplying TrkA receptors to axons, specifically during development, and highlight the physiological relevance of this axon targeting mechanism in the nervous system. |
