Roles of channels and receptors in the growth cone during PNS axonal regeneration

Abstract

Neurons in the peripheral nervous system (PNS) are known to maintain a regenerative capacity and will normally regenerate their axons within a permissive growth environment. The success of regeneration in the PNS largely depends on maintenance of the supportive basal lamina membrane, efficient removal of axonal and myelin debris by macrophages and Schwann cells, expression of neurotrophic factors by Schwann cells, and up-regulation of the intrinsic growth program in PNS neurons. The PNS regenerative process is well characterized through initial Wallerian degeneration followed by axonal sprouting, formation of neuronal growth cones, active axonal growth to the target, and finally sensory and motor functional recovery. The initiation and maintenance of active growth cones during peripheral nerve regeneration recapitulates many aspects of early neural development and is achieved through the activation of complex signaling cascades, involving various receptors, channels, cytoplasmic signaling cascades, as well as transcriptional and translational programs. This review focuses on roles of cell surface ion channels and receptors in the growth cone during Wallerian degeneration and axon regeneration in the PNS.

A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program

“…During regeneration, many genes are dynamically down-regulated (Shim and Ming, 2010). To specifically identify TFs that could regulate this process, we screened for experimentally validated TFBS over-represented in modules down-regulated after injury—purple, dark red, and green-yellow (candidate transcriptional repressors; Experimental Procedures), which are enriched in genes related to the GO terms plasma membrane, ion/gated channel, ion binding, and synapse/cell junction related (Table S3).…”

Axon Regeneration Pathways Identified by Systematic Genetic Screening in C. elegans

“…Notably, regrowth did not require genes involved in GABA vesicular packaging ( unc-46, unc-47 ) or the postsynaptic muscle GABA receptor ( unc-49 ). GABA has nonsynaptic growth-promoting roles in vertebrate neuronal development (Akerman and Cline, 2007) and a trophic role in regenerating vertebrate neurons (Shim and Ming, 2010; Toyoda et al, 2003). Speculatively, regenerating neurons may become more dependent on trophic factors whose roles in development are masked by genetic redundancy.…”

Redox-guided axonal regrowth requires cyclic GMP dependent protein kinase 1: Implication for neuropathic pain

“…Peripheral neurons have the inherent capacity to regrow and eventually re-innervate the target if the correct path is not lost, a prerequisite that depends on a complex network of guidance cues and intact myelin sheaths [1], [2]. It is believed that successful re-innervation leads to pain resolution [3] whereas aberrant growth and sprouting increases pathological spontaneous activity and hyperexcitability [4], [5].…”