Attractive and repulsive factors act through multi-subunit receptor complexes to regulate nerve fiber growth

Abstract

In the nervous system, attractive and repulsive factors guide neuronal growth, pathfinding and target innervation during development, learning and regeneration after injury. Repulsive and growth-inhibitory factors, such as some ephrins, semaphorins, netrins and myelin-associated growth inhibitors, restrict nerve fiber growth, whereas neurotrophins, and other ephrins, semaphorins and netrins attract fibers and promote neurite growth. Several of these guidance molecules also play crucial roles in vasculogenesis, and regulate cell migration and tissue formation in different organs. Precise and highly specific signal transduction in space and time is required in all these cases, which primarily depends on the presence and function of specific receptors. Interestingly, many of these ligands act through multi-subunit receptor complexes. In this Commentary, we review the current knowledge of how complexes of the receptors for attractive and repulsive neurite growth regulatory factors are reorganized in a spatial and temporal manner, and reveal the implications that such dynamics have on the signaling events that coordinate neurite fiber growth.

Transcriptomic Profiling Discloses Molecular and Cellular Events Related to Neuronal Differentiation in SH-SY5Y Neuroblastoma Cells

“…Specifically, we identified transcriptional changes for many semaphorin (SEMA3A, 3D, 3F, 4G, 5A, 6A, 6C, and 6D) and related plasma membrane receptors (PLXNA2, PLXND1 and NRP1). Semaphorins exert their effects by finely regulating the balance between attraction and repulsion of growing axons in neuronal cells, as reported in both in vitro and in vivo models (Thiede-Stan and Schwab 2015;Zhou et al 2008). We ascertained the expression of SEMA3A protein by immunoblotting and detected an increased expression of the secreted 65-kDa isoform (Antipenko et al 2003;Tran et al 2007).…”

Transcriptomic analysis of gingival mesenchymal stem cells cultured on 3D bioprinted scaffold: A promising strategy for neuroregeneration

“…The process of neurite growth is very complex and is regulated by attractive and repulsive factors. Moreover, the precise switch from an attractive to a repulsive behavior is necessary for axonal growth . While neurotrophins mediated neurite outgrowth and differentiation, ephrin–ephrin receptors (Ephrin‐eph) signaling mediates short range cell–cell communication and can induce both attractive and repulsive interactions.…”

Tetraspanin-3 is an organizer of the multi-subunit Nogo-A signaling complex

“…Such dynamic multi-subunit receptor complex (Thiede-Stan and Schwab, 2015) assemblies in the presence of a ligand are known for other regulators of neurite growth -e.g. the neurotrophins BDNF and NGF, or myelin associated glycoprotein (MAG) (Ascano et al, 2009;Haapasalo et al, 2002;Marchetti et al, 2013;Vermehren-Schmaedick et al, 2014;Wong et al, 2002).…”

“…Nogo-A restricts neurite outgrowth through two different domains -Nogo-66 (rat, amino acid residues 1026-1091) and Nogo-A-Δ20 (rat, amino acid residues 544-725; part of the 'aminoNogo' domain) (Chen et al, 2000;GrandPré et al, 2000;Oertle et al, 2003;Schwab, 2010). In vivo, full-length Nogo-A might undergo transcytosis or proteolytic cleavage, resulting in the release of active fragments such as Nogo-A-Δ20 (Joset et al, 2010;Kempf et al, 2014;Thiede-Stan and Schwab, 2015). In the developing CNS, Nogo-A-Δ20 promotes the migration of neuronal precursors but inhibits primary brain microvascular endothelial cell migration, as well as the spreading of endothelial cells and fibroblasts (Kempf et al, 2014;Mathis et al, 2010;Oertle et al, 2003;Rolando et al, 2012;Schmandke et al, 2013;Walchli et al, 2013).…”