Agrin Acts via a MuSK Receptor Complex

TLDR

Neuromuscular junction formation depends on reciprocal nerve–muscle interactions, with agrin as a nerve‑derived factor that induces motor endplate reorganization but whose mechanism is poorly understood, and MuSK, a receptor tyrosine kinase localized to the endplate, positioned to receive this signal. Mice lacking agrin or MuSK exhibit similar neuromuscular junction defects, showing that agrin signals through a receptor complex that includes MuSK and a myotube‑specific accessory component.

Abstract

Formation of the neuromuscular junction depends upon reciprocal inductive interactions between the developing nerve and muscle, resulting in the precise juxtaposition of a differentiated nerve terminal with a highly specialized patch on the muscle membrane, termed the motor endplate. Agrin is a nerve-derived factor that can induce molecular reorganizations at the motor endplate, but the mechanism of action of agrin remains poorly understood. MuSK is a receptor tyrosine kinase localized to the motor endplate, seemingly well positioned to receive a key nerve-derived signal. Mice lacking either agrin or MuSK have recently been generated and exhibit similarly profound defects in their neuromuscular junctions. Here we demonstrate that agrin acts via a receptor complex that includes MuSK as well as a myotube-specific accessory component.