Journal: Glycobiology
Article Title: Dystroglycan-HSPG interactions provide synaptic plasticity and specificity
doi: 10.1093/glycob/cwae051
Figure Lengend Snippet: Schematic depiction of the structural organization of the dystroglycan laminin receptor showing it’s covalently linked α and β domains, extensive glycosylation of the α-domain, and sarcospan, sarcoglycan glycoproteins and stretch receptors that interact with the αDG domain. βDG interactive cytoplasmic proteins including dystrophin, plectin, dystrobrevin, syntrophin form an organizational instructive scaffold of importance in cell signaling. This scaffold interfaces with the actin cytoskeleton which transfers cyclic stretching and relaxation that regulates extracellular signal-regulated kinase 1/2 (ERK1/2) cell signaling. An influx of Ca2+ through stretch activated ion-channels regulate neuronal nitric oxide synthase (nNOS) activity, a signaling molecule that provides synaptic plasticity. This also regulates the cerebrovasculature of the neurovascular unit in the CNS/PNS and regulates brain perfusion. Plectin has actin, dystrophin, integrin and βDG binding sites and forms an interactive instructional scaffold with important roles in cell-signaling. βDG also has a binding site for yes associated protein (YAP), a transcription factor effector of the hippo cell signaling pathway. This is a mechanosensitive cell signaling pathway that regulates tissue composition, aids in the homeostasis of tissues and also regulates the final size attained by organs in maturity.
Article Snippet: Agrin , Assembly and function of NMJ, regulation of cardiomyocyte function, bioresponsive mechanoreceptor regulated by Hippo cell signaling , Agrin initiates MuSK kinase activity, a receptor tyrosine kinase and a key regulator of NMJ development. Agrin interacts with LRPR, rapsyn and DOK-7 cytoplasmic adaptor protein ( ). The NMJ agrin-Lrp4-MuSK cell signaling pathway ( ) is disrupted in congenital myasthenia syndromes, Schwartz-Jampel syndrome, Fukuyama-type congenital muscular dystrophy, amyotrophic lateral sclerosis, and sarcopenia. Impaired MuSK signaling causes severe muscle weakness in congenital myasthenic syndromes. DOK7 promotes NMJ regeneration after nerve injury , neuronal agrin promotes myoblast proliferation( ). Neuronal LRP4 regulates synapse formation and synaptic plasticity ( ). Mechanosensitive Yap/Taz effectors of Hippo cell signaling regulate cardiomyocyte replication/regeneration through Agrin. .
Techniques: Activity Assay, Binding Assay