Dystroglycan is a binding protein of laminin and merosin in peripheral nerve

Abstract

a-Dystroglycan, a 156 kDa dystrophin-associated glycoprotein, binds laminin in skeletal muscle. Here we demonstrate that a-dystroglycan is a binding protein of laminin (AIBlIB2) and merosin (MIBlIB2) in peripheral nerve. Immunocytochemical analysis demonstrates the localization of a-dystroglycan and merosin surrounding myelin sheath of peripheral nerve fibers. Biochemical analysis demonstrates that the 120 kDa peripheral nerve a-dystroglycan binds merosin as well as laminin. The binding of laminin and merosin is Ca*' dependent and is inhibited by NaCl and heparin. Recently, merosin was shown to be deficient in the peripheral nerve of dy mice which have defects in myelination. The interaction between a-dystroglycan and merosin may play a role in the regulation of Schwann cell myelination and/or maintenance of myelin sheath.

Activation of Muscle-specific Receptor Tyrosine Kinase and Binding to Dystroglycan Are Regulated by Alternative mRNA Splicing of Agrin

“…Another function that involves the LG domains of agrin is the binding to ␣-dystroglycan, a peripheral membrane protein that is tightly associated with the transmembranous ␤-dystroglycan and arises from a common precursor protein by posttranslational cleavage (33). Binding to ␣-dystroglycan has also been found in other LG domain-containing proteins such as laminin-␣1 and -␣2 (33)(34)(35), perlecan (35), and neurexins (36). Although initially postulated, binding of agrin to ␣-dystroglycan is not necessary for its AChR-aggregating activity (23).…”

Developmental Expression of the Neuron-specific N-Acetylglucosaminyltransferase Vb (GnT-Vb/IX) and Identification of Its in Vivo Glycan Products in Comparison with Those of Its Paralog, GnT-V

“…␣-Dystroglycan binds with high affinity to several extracellular matrix components, laminin, agrin, and neurexin (32,(35)(36)(37)(38), and it is heavily glycosylated with O-linked mannosyl glycans (39 -43). Mutations in POMT1, POMT2, POMGnT1, and LARGE lead to altered glycosylation of ␣-dystroglycan with abolished laminin binding activity and are believed to be a major underlying mechanism of muscular dystrophy and type II lissencephaly (10, 44 -46).…”

Dystrophin and utrophin isoforms are expressed in glia, but not neurons, of the avian parasympathetic ciliary ganglion

“…These multimolecular complexes have two major functions: 1) provide structural anchorage and adhesion by linking the actin cytoskeleton to the basal lamina; and 2) localize specific ion channels and signaling molecules to precise surface membrane regions (Matsumura et al, 1993;Yamada et al, 1994;Saito et al, 1999;Imamura et al, 2000;Masaki et al, 2001;Haenggi et al, 2004). In peripheral nerve, Dp116 and full-length utrophin provide structural support to the outer surface membrane of Schwann cells by linking the actin cytoskeleton and basal lamina (Yamada et al, 1994;Saito et al, 1999;Imamura et al, 2000;Saito et al, 2003). Demyelinating neuropathy has been seen in dystrophic patients with loss of Dp116 (Comi et al, 1995), and myelin instability occurs in animal models in which the dystrophin complex is disrupted (Saito et al, 2003;Cai et al, 2007).…”