Retrograde Transportation of Neurotrophin Receptors as Signal to the Cell Body

Unlike most other internalized receptors, which are usually degraded after internalization, neurotrophin-Trk complexes in endocytotic vesicles function as signal transducers and provide a mechanism for long-range signaling in the neuronal cytoplasm. Several studies have provided support for the retrograde transportation model of neurotrophin-Trk complexes; these studies indicate that endocytotic vesicles containing neurotrophin-Trk complexes may be functionally active and should be viewed as activated signaling complexes that spread the cytosolic signaling of neurotrophin-Trk complexes to distant parts of the neuron via active transport mechanisms. Intriguingly, as has been shown with another tyrosine kinase (ErbB4 receptor tyrosine kinase), other hitherto unappreciated mechanisms, such as cleavage of receptor fragments, may also be operative in trafficking signals from extracellular receptors to intracellular and nuclear targets (Ni et al. 2001). Whether such novel signaling mechanisms are also utilized by neurotrophin receptors will undoubtedly be the focus of considerable future research.

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