A stoichiometric complex of neurexins and dystroglycan in brain

Citation
S. Sugita et al., A stoichiometric complex of neurexins and dystroglycan in brain, J CELL BIOL, 154(2), 2001, pp. 435-445
Citations number
61
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
154
Issue
2
Year of publication
2001
Pages
435 - 445
Database
ISI
SICI code
0021-9525(20010723)154:2<435:ASCONA>2.0.ZU;2-L
Abstract
In nonneuronal cells, the cell surface protein dystroglycan links the intra cellular cytoskeleton (via dystrophin or utrophin) to the extracellular mat rix (via laminin, agrin, or perlecan). Impairment of this linkage is instru mental in the pathogenesis of muscular dystrophies. In brain, dystroglycan and dystrophin are expressed on neurons and astrocytes, and some muscular d ystrophies cause cognitive dysfunction; however, no extracellular binding p artner for neuronal dystroglycan is known. Regular components of the extrac ellular matrix, such as laminin, agrin, and perlecan, are not abundant in b rain except in the perivascular space that is contacted by astrocytes but n ot by neurons, suggesting that other ligands for neuronal dystroglycan must exist. We have now identified alpha- and beta -neurexins, polymorphic neur on-specific cell surface proteins, as neuronal dystro-glycan receptors. The extracellular sequences of alpha- and beta -neurexins are largely composed of laminin-neurexin-sex hormone-binding globulin (LNS)/laminin G domains, which are also found in laminin, agrin, and perlecan, that are dystroglycan ligands. Dystroglycan binds specifically to a subset of the LNS domains of neurexins in a tight interaction that requires glycosylation of dystroglyc an and is regulated by alternative splicing of neurexins. Neurexins are rec eptors fr the excitatory neurotoxin alpha -latrotoxin; this toxin competes with dystroglycan for binding, suggesting overlapping binding sites on neur exins for dystroglycan and alpha -latrotoxin. Our data indicate that dystro glycan is a physiological ligand for neurexins and that neurexins' tightly regulated interaction could mediate cell adhesion between brain cells.