Structural Perspectives on Axon Guidance

Annu Rev Cell Dev Biol. 2016 Oct 6:32:577-608. doi: 10.1146/annurev-cellbio-111315-125008. Epub 2016 Aug 24.

Abstract

Axon guidance relies on a combinatorial code of receptor and ligand interactions that direct adhesive/attractive and repulsive cellular responses. Recent structural data have revealed many of the molecular mechanisms that govern these interactions and enabled the design of sophisticated mutant tools to dissect their biological functions. Here, we discuss the structure/function relationships of four major classes of guidance cues (ephrins, semaphorins, slits, netrins) and examples of morphogens (Wnt, Shh) and of cell adhesion molecules (FLRT). These cell signaling systems rely on specific modes of receptor-ligand binding that are determined by selective binding sites; however, defined structure-encoded receptor promiscuity also enables cross talk between different receptor/ligand families and can also involve extracellular matrix components. A picture emerges in which a multitude of highly context-dependent structural assemblies determines the finely tuned cellular behavior required for nervous system development.

Keywords: FLRT; ephrin; morphogen; netrin; semaphorin; slit.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axon Guidance*
  • Humans
  • Models, Biological
  • Nerve Tissue Proteins / metabolism*
  • Receptors, Cell Surface / metabolism
  • Signal Transduction

Substances

  • Nerve Tissue Proteins
  • Receptors, Cell Surface