A lipid-protein hybrid model for tight junction

1 Nephrology Section and Epithelial Biology Laboratory, Veterans Affairs Greater Los Angeles Healthcare System (Veterans Integrated Services Network 22), 2 Nephrology Division, Rancho Los Amigos Medical Center, and 3 David Geffen School of Medicine, University of California, Los Angeles, California Submitted 31 July 2008 ; accepted in final form 11 August 2008 ABSTRACT The epithelial tight junction (TJ) was first described ultrastructurally as a fusion of the outer lipid leaflets of the adjoining cell membrane bilayers (hemifusion). The discovery of an increasing number of integral TJ and TJ-associated proteins has eclipsed the original lipid-based model with the wide acceptance of a protein-centric model for the TJ. In this review, we stress the importance of lipids in TJ structure and function. A lipid-protein hybrid model accommodates a large body of information supporting the lipidic characteristics of the TJ, harmonizes with the accumulating evidence supporting the TJ as an assembly of lipid rafts, and focuses on an important, but relatively unexplored, field of lipid-protein interactions in the morphology, physiology, and pathophysiology of the TJ. lipid rafts; lipid leaflets; claudins; hemifusion Address for reprint requests and other correspondence: D. B. N. Lee, Dept. of Medicine (111), VA Medical Center, 16111 Plummer St., North Hills, CA 91343 (e-mail: dbnlee{at}ucla.edu )