Regulation of eye size by the retinal basement membrane and vitreous body.

Purpose: Congenital high myopia is an early-onset enlargement of the eye globes that carries a high risk for retinal detachment. The genetic basis for congenital high myopia has frequently been connected to mutations in genes encoding extracellular matrix proteins of the vitreous body (VB) and the inner limiting membrane (ILM). Why defective or missing VB and ILM proteins lead to an increase in eye size is unknown.

Glycosaminoglycan-dependent and -independent inhibition of neurite outgrowth by agrin.

Agrin is a proteoglycan that can inhibit neurite outgrowth from multiple neuronal types when present as a substrate. Agrin's neurite inhibitory activity is confined to the N-terminal segment of the protein (agrin N150), which contains heparan sulfate (HS) and chondroitin sulfate (CS) side chains. We have examined the activities of various purified recombinant agrin fragments and their glycosaminoglycan (GAG) side chains in neurite outgrowth inhibition.

Agrin is a chimeric proteoglycan with the attachment sites for heparan sulfate/chondroitin sulfate located in two multiple serine-glycine clusters.

Agrin is a large extracellular matrix protein that plays a key role in the formation and maintenance of the vertebrate neuromuscular junction. The amino acid sequence of agrin encodes a protein with a molecular size of 220 kDa, whereas SDS-PAGE shows a diffuse band around 400 kDa. Further studies showed that agrin is highly glycosylated and belongs to the family of heparan sulfate proteoglycans.

Mapping of the laminin-binding site of the N-terminal agrin domain (NtA).

Agrin is a key organizer of acetylcholine receptor (AChR) clustering at the neuromuscular junction. The binding of agrin to laminin is required for its localization to synaptic basal lamina and other basement membranes. The high-affinity interaction with the coiled-coil domain of laminin is mediated by the N-terminal domain of agrin.