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Journal of Virology, October 2005, p. 12528-12535, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12528-12535.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Transmembrane Domain of the Respiratory Syncytial Virus F Protein Is an Orientation-Independent Apical Plasma Membrane Sorting Sequence

Sean C. Brock,1,2 Josh M. Heck,2 Patricia A. McGraw,2 and James E. Crowe Jr.1,2*

Departments of Microbiology and Immunology,1 Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 372322

Received 8 February 2005/ Accepted 29 April 2005

The processes that facilitate transport of integral membrane proteins though the secretory pathway and subsequently target them to particular cellular membranes are relevant to almost every field of biology. These transport processes involve integration of proteins into the membrane of the endoplasmic reticulum (ER), passage from the ER to the Golgi, and post-Golgi trafficking. The respiratory syncytial virus (RSV) fusion (F) protein is a type I integral membrane protein that is uniformly distributed on the surface of infected nonpolarized cells and localizes to the apical plasma membrane of polarized epithelial cells. We expressed wild-type or altered RSV F proteins to gain a better understanding of secretory transport and plasma membrane targeting of type I membrane proteins in polarized and nonpolarized epithelial cells. Our findings reveal a novel, orientation-independent apical plasma membrane targeting function for the transmembrane domain of the RSV F protein in polarized epithelial cells. This work provides a basis for a more complete understanding of the role of the transmembrane domain and cytoplasmic tail of viral type I integral membrane proteins in secretory transport and plasma membrane targeting in polarized and nonpolarized cells.

* Corresponding author. Mailing address: Vanderbilt University Medical Center, T-2220 Medical Center North, Division of Pediatric Infectious Diseases, 1161 21st Ave. South, Nashville, TN 37232-2905. Phone: (615) 343-8064. Fax: (615) 343-8055. E-mail: james.crowe{at}vanderbilt.edu.

Journal of Virology, October 2005, p. 12528-12535, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12528-12535.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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