title: The role of the extracellular domain in the biology of the coxsackievirus and adenovirus receptor.
abstract: The Coxsackievirus B and Adenovirus Receptor (CAR) plays a dual role as a homotypic junctional adhesion protein and as a viral receptor. CAR is a transmembrane protein and a member of the Immunoglobulin (Ig) superfamily with two extracellular Ig-like domains. The most distal Ig-like domain (D1) mediates the homophilic interaction and is also responsible for the high-affinity binding of the adenovirus (Ad) fiber protein. Currently, no activity has been ascribed to the proximal Ig-like domain (D2). To further understand the function of the extracellular domain in the biological activities of CAR, we created extracellular deletion mutants and evaluated cellular localization, adhesion, and viral infection. Deletion of any segment of the extracellular domain results in loss of adhesion and mislocalization as explained by a model, termed "diffusion trapping," that suggests adhesion is the driving force in junctional localization. Loss of junctional localization and adhesion was particularly apparent in polarized human airway epithelia, where mutant CAR expression was basolateral but not limited to the lateral junctions between cells. Surprisingly, the D2 domain was required for adenovirus fiber-knob binding and infection. In summary, the entire extracellular domain of CAR is of vital importance to the biology of this highly conserved and important protein.
authors.affiliation: Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, 440 EMRB, Iowa City, IA 52242, USA.
authors.forename: Katherine J D A
authors.initials: KJ
authors.lastname: Excoffon
authors.forename: Geri L
authors.initials: GL
authors.lastname: Traver
authors.forename: Joseph
authors.initials: J
authors.lastname: Zabner
mesh_terms: D000257:Adenoviridae Infections / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002448:Cell Adhesion / Q000502:physiology; D002522:Chlorocebus aethiops; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D006224:Cricetinae; D005110:Extracellular Space; D017353:Gene Deletion; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016296:Mutagenesis; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000502:physiology*
chemical_list: C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D008565:Membrane Proteins; D011991:Receptors, Virus