The role of the extracellular domain in the biology of the coxsackievirus and adenovirus receptor

Katherine J D A Excoffon; Geri L Traver; Joseph Zabner

doi:10.1165/rcmb.2005-0031OC

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The role of the extracellular domain in the biology of the coxsackievirus and adenovirus receptor

Journal article

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Peer reviewed

The role of the extracellular domain in the biology of the coxsackievirus and adenovirus receptor

Katherine J D A Excoffon, Geri L Traver and Joseph Zabner

American journal of respiratory cell and molecular biology, Vol.32(6), pp.498-503

06/2005

DOI: 10.1165/rcmb.2005-0031OC

PMCID: PMC2715320

PMID: 15778494

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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.

Protein Structure, Tertiary

Adenoviridae Infections - pathology

Cricetinae

Respiratory Mucosa - cytology

Membrane Proteins - genetics

Receptors, Virus - metabolism

Humans

Intercellular Junctions - metabolism

Cercopithecus aethiops

Coxsackie and Adenovirus Receptor-Like Membrane Protein

Extracellular Space

Receptors, Virus - genetics

Adenoviridae Infections - physiopathology

Animals

Receptors, Virus - chemistry

Membrane Proteins - chemistry

Mutagenesis

Cell Adhesion - physiology

Gene Deletion

Respiratory Mucosa - physiology

Membrane Proteins - metabolism

COS Cells

CHO Cells

Details

Title: Subtitle: The role of the extracellular domain in the biology of the coxsackievirus and adenovirus receptor
Creators: Katherine J D A Excoffon - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, 440 EMRB, Iowa City, IA 52242, USA
Geri L Traver
Joseph Zabner
Resource Type: Journal article
Publication Details: American journal of respiratory cell and molecular biology, Vol.32(6), pp.498-503
DOI: 10.1165/rcmb.2005-0031OC
PMID: 15778494
PMCID: PMC2715320
NLM abbreviation: Am J Respir Cell Mol Biol
ISSN: 1044-1549
eISSN: 1535-4989
Grant note: HL51670-11 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS DK54759 / NIDDK NIH HHS
Language: English
Date published: 06/2005
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984094335602771

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