Journal Article

Dystroglycan is a scaffold for extracellular axon guidance decisions

Lindenmaier, L Bailey, Wright, Kevin M, Parmentier, Nicolas, Guo, Caiying, Tissir, Fadel

2019

Overview

Axon guidance requires interactions between extracellular signaling molecules and transmembrane receptors, but how appropriate context-dependent decisions are coordinated outside the cell remains unclear. Here we show that the transmembrane glycoprotein Dystroglycan interacts with a changing set of environmental cues that regulate the trajectories of extending axons throughout the mammalian brain and spinal cord. Dystroglycan operates primarily as an extracellular scaffold during axon guidance, as it functions non-cell autonomously and does not require signaling through its intracellular domain. We identify the transmembrane receptor Celsr3/Adgrc3 as a binding partner for Dystroglycan, and show that this interaction is critical for specific axon guidance events in vivo. These findings establish Dystroglycan as a multifunctional scaffold that coordinates extracellular matrix proteins, secreted cues, and transmembrane receptors to regulate axon guidance.

• Publisher: eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Amino Acid Motifs / Amino Acid Sequence / Animals / Axon guidance / Axon Guidance - physiology / Axons - physiology / Brain - physiology / Cadherins - chemistry / Cadherins - metabolism / celsr3 / Celsr3 protein / commissural axon / Dystroglycan / Dystroglycans - metabolism / Extracellular matrix / Extracellular Space - physiology / internal capsule / Intracellular signalling / Ligands / Localization / Mice / Nervous system / Neuroepithelial Cells - metabolism / Neuroscience / Protein Binding / Proteins / Receptors, Cell Surface - chemistry / Receptors, Cell Surface - metabolism / Spinal cord / Statistical analysis