Isoform-specific regulation and localization of the coxsackie and adenovirus receptor in human airway epithelia

Katherine J D A Excoffon; Nicholas D Gansemer; Matthew E Mobily; Philip H Karp; Kalpaj R Parekh; Joseph Zabner

doi:10.1371/journal.pone.0009909

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Isoform-specific regulation and localization of the coxsackie and adenovirus receptor in human airway epithelia

Journal article

Open access

Peer reviewed

Isoform-specific regulation and localization of the coxsackie and adenovirus receptor in human airway epithelia

Katherine J D A Excoffon, Nicholas D Gansemer, Matthew E Mobily, Philip H Karp, Kalpaj R Parekh and Joseph Zabner

PloS one, Vol.5(3), pp.e9909-e9909

03/26/2010

DOI: 10.1371/journal.pone.0009909

PMCID: PMC2845650

PMID: 20361046

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Abstract

Adenovirus is an important respiratory pathogen. Adenovirus fiber from most serotypes co-opts the Coxsackie-Adenovirus Receptor (CAR) to bind and enter cells. However, CAR is a cell adhesion molecule localized on the basolateral membrane of polarized epithelia. Separation from the lumen of the airways by tight junctions renders airway epithelia resistant to inhaled adenovirus infection. Although a role for CAR in viral spread and egress has been established, the mechanism of initial respiratory infection remains controversial. CAR exists in several protein isoforms including two transmembrane isoforms that differ only at the carboxy-terminus (CAR(Ex7) and CAR(Ex8)). We found low-level expression of the CAR(Ex8) isoform in well-differentiated human airway epithelia. Surprisingly, in contrast to CAR(Ex7), CAR(Ex8) localizes to the apical membrane of epithelia where it augments adenovirus infection. Interestingly, despite sharing a similar class of PDZ-binding domain with CAR(Ex7), CAR(Ex8) differentially interacts with PICK1, PSD-95, and MAGI-1b. MAGI-1b appears to stoichiometrically regulate the degradation of CAR(Ex8) providing a potential mechanism for the apical localization of CAR(Ex8) in airway epithelial. In summary, apical localization of CAR(Ex8) may be responsible for initiation of respiratory adenoviral infections and this localization appears to be regulated by interactions with PDZ-domain containing proteins.

Protein Structure, Tertiary

Cricetinae

Cricetulus

Epithelium - metabolism

Receptors, Virus - biosynthesis

Humans

Gene Expression Regulation

Cercopithecus aethiops

Trachea - metabolism

Coxsackie and Adenovirus Receptor-Like Membrane Protein

Receptors, Virus - genetics

RNA, Messenger - metabolism

Animals

Protein Isoforms

Bronchi - metabolism

Adenoviridae Infections - metabolism

Cell Differentiation

Cell Membrane - metabolism

Mice

COS Cells

CHO Cells

Details

Title: Subtitle: Isoform-specific regulation and localization of the coxsackie and adenovirus receptor in human airway epithelia
Creators: Katherine J D A Excoffon - Department of Biological Sciences, Wright State University, Dayton, Ohio, United States of America
Nicholas D Gansemer
Matthew E Mobily
Philip H Karp
Kalpaj R Parekh
Joseph Zabner
Resource Type: Journal article
Publication Details: PloS one, Vol.5(3), pp.e9909-e9909
DOI: 10.1371/journal.pone.0009909
PMID: 20361046
PMCID: PMC2845650
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Grant note: P01 HL051670 / NHLBI NIH HHS HL51670-11 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS DK54759 / NIDDK NIH HHS
Language: English
Date published: 03/26/2010
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Anatomy and Cell Biology; Surgery; Cardiothoracic Surgery; Internal Medicine
Record Identifier: 9984094357502771

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