Membrane turnover and receptor trafficking in regenerating axons

Abstract

Peripheral axonal regeneration requires surface-expanding membrane addition. The continuous incorporation of new membranes into the axolemma allows the pushing force of elongating microtubules to drive axonal growth cones forwards. Hence, a constant supply of membranes and cytoskeletal building blocks is required, often for many weeks. In human peripheral nerves, axonal tips may be more than 1 m away from the neuronal cell body. Therefore, in the initial phase of regeneration, membranes are derived from pre-existing vesicles or synthesised locally. Only later stages of axonal regeneration are supported by membranes and proteins synthesised in neuronal cell bodies, considering that the fastest anterograde transport mechanisms deliver cargo at 20 cm/day. Whereas endocytosis and exocytosis of membrane vesicles are balanced in intact axons, membrane incorporation exceeds membrane retrieval during regeneration to compensate for the loss of membranes distal to the lesion site. Physiological membrane turnover rates will not be established before the completion of target reinnervation. In this review, the current knowledge on membrane traffic in axonal outgrowth is summarised, with a focus on endosomal vesicles as the providers of membranes and carriers of growth factor receptors required for initiating signalling pathways to promote the elongation and branching of regenerating axons in lesioned peripheral nerves.

The molecular mechanisms underlying lens fiber elongation

“…In neurons and other cell types, such membrane growth occurs via release of membranous vesicles from the endoplasmic reticulum/Golgi network, and trafficking of these vesicles to their site of membrane insertion. In neurons, it is established that such trafficking is, in part, driven by microtubules in partnership with motor proteins of the kinesin/dynein families which are able to move vesicular cargos to cellular locations distant from their synthesis (Hausott and Klimaschewski, 2015). While this mechanism has not been functionally investigated in the lens, the microtubules of elongating lens fiber cells are closely associated with the Golgi network in the central region of these cells, and contact numerous vesicles throughout the lens fiber, suggesting that microtubules can transport vesicular cargos necessary to increase fiber cell membrane area during cellular elongation (Lo et al, 2003).…”

A new front in cell invasion: The invadopodial membrane

“…Examples of directed membrane trafficking include include neurite outgrowth (Hausott and Klimaschewski, 2016), neuronal and immunological synapse function (Gonnord et al, 2012), wound healing (Abreu-Blanco et al, 2011), cell division (Shuster and Burgess, 2002), and cell migration (Maritzen et al, 2015). Targeted vesicle delivery requires a source of internal vesicles/membrane, exocytic trafficking machinery, and when vesicles are dynamically recycled, endocytic recycling components (Grant and Donaldson, 2009).…”

Actions of quercetin, a flavonoid, on ion transporters: its physiological roles

“…Neurite elongation is one of the most important factors for the development of neural circuits. The molecular mechanisms of neurite elongation have been studied from various points of view . The supply of various materials to the neurite tip plays an important role in neurite elongation and membrane expansion .…”

“…The supply of various materials to the neurite tip plays an important role in neurite elongation and membrane expansion . It is a key point for understanding the process to clarify the molecular mechanisms by which components required for expansion of membrane surfaces are added to tips of neurite, since the continuous incorporation of new membranes into neurite tips is required to regenerate peripheral axons, which is also associated with polymerization of microtubules . Microtubules are one of major cytoskeleton elements, and a reversible association process involving polymerization and depolymerization of tubulin forms microtubules .…”