title: Alpha7beta1 integrin is a receptor for laminin-2 on Schwann cells.
abstract: The Schwann cell basal lamina acts as an organizer of peripheral nerve tissue and influences many aspects of cell behavior during development and regeneration. A principal component of the Schwann cell basal lamina is laminin-2. This study was undertaken to identify Schwann cell receptors for laminin-2. We found that among several Schwann cell integrins that can potentially interact with laminin-2, only alpha7beta1 bound to laminin-2-Sepharose. Dystroglycan, a non-integrin Schwann cell receptor for laminin-2 identified previously, was also found to bind to laminin-2-Sepharose. Antibody to the alpha7 integrin subunit partially inhibited Schwann cell adhesion to laminin-2. Small interfering RNA-mediated suppression of either alpha7 integrin or dystroglycan expression decreased adhesion and spreading of Schwann cells on laminin-2, whereas knocking down both proteins together inhibited adhesion and spreading on laminin-2 almost completely. alpha7 integrin and dystroglycan both colocalized with laminin-2 containing basal lamina tubes in differentiating neuron-Schwann cell cocultures. The alpha7beta1 integrin also coprecipitates with focal adhesion kinase in differentiating cocultures. These findings strongly suggest that alpha7beta1 integrin is a Schwann cell receptor for laminin-2 that provides transmembrane linkage between the Schwann cell basal lamina and cytoskeleton.
authors.affiliation: Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania, USA. mchernousov@geisinger.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Chernousov
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kaufman
authors.forename: Richard C
authors.initials: RC
authors.lastname: Stahl
authors.forename: Katrina
authors.initials: K
authors.lastname: Rothblum
authors.forename: David J
authors.initials: DJ
authors.lastname: Carey
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019138:Antibodies, Blocking / Q000494:pharmacology; D001710:Biotin / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002846:Chromatography, Affinity; D018920:Coculture Techniques; D049030:Dystroglycans / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D039121:Integrin alpha6beta1 / Q000502:physiology; D016023:Integrins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000378:metabolism*; D014162:Transfection
chemical_list: D019138:Antibodies, Blocking; D039121:Integrin alpha6beta1; D016023:Integrins; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D049030:Dystroglycans; D001710:Biotin; D051417:Focal Adhesion Kinase 1; C082908:integrin alpha7beta1