The substructure of tight junctions is investigated by direct freezing techniques that avoid any chemical fixation and serve to increase the resolution of individual membrane components. The backbone of the tight junction of each of the paired component membranes is a continuous cylinder. This model replaces the previous view that tight junctions are comprised of rows of intramembrane proteins; the rod-shaped structures are now interpreted as inverted cylindrical micelles of membrane lipids. Evidence for this model is also being gathered from investigations of pure lipid bilayer systems which are induced to form non-planar micellar phases by addition of calcium ion. Cylindrical micelles identical to those seen at tight junctions are found embedded in these lipid bilayers. Tight junctions but no septate junctions, in invertebrates appear to have lipidic backbones. How tight junctions serve in the blood-brain barrier system to prevent small charged solutes from entering the brain is made clear by this new model of tight junction structure. Gap junctions form within minutes of incubation of prostate slices in certain media, even when it contains metabolic inhibitors. This result suggests that precursors of the intramembranous component of gap junctions preexist in the cell membrane.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS001442-05
Application #
4696785
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code