Molecular mechanisms regulating the retrograde axonal transport of neurotrophins

Neurotrophins are released from target tissues following neural innervation and bind to specific receptors situated on the nerve terminal plasma membr ane. The neurotrophin-receptor complex undergoes retrograde axonal transpor t towards the cell soma, where it signals to the nucleus. This process allo ws neurotrophins to perform their numerous functions, which include the pro motion of neuronal survival and the outgrowth of axons towards certain targ et tissues. The molecular events controlling each of the components of retr ograde axonal transport are beginning to become defined. There is good evid ence for the participation of phosphatidylinositol 3-kinase, phosphatidylin ositol 4-kinase and the actin cytoskeleton in neurotrophin retrograde axona l transport in vivo. It also appears that the retrograde motor protein dyne in mediates the retrograde axonal transport in vivo of neurotrophins such a s nerve growth factor. This review discusses the role of the neurotrophin r eceptors in binding and axonal transport, the endocytic processes required for neurotrophin internalization, the targeting and trafficking of neurotro phins, and the propagation of neurotrophin-induced signals along the axon. (C) 1000 Elsevier Science B.V. All rights reserved.