Junctin is a 26 kDa membrane protein that binds to calsequestrin, triadin, and 
ryanodine receptors (RyRs) within the junctional sarcoplasmic reticulum of 
calcium release units. The sequence of junctin includes a short N-terminal 
cytoplasmic domain a single transmembrane domain, and a highly charged 
C-terminal domain located in the sarcoplasmic reticulum lumen. Dog and mouse 
junctins are highly conserved at the transmembrane domains, but the luminal 
domains are more divergent. To probe the contribution of junctin to the 
architecture of calcium release units in heart, we engineered transgenic mice 
overexpressing canine junctin and examined the left ventricular myocardium by 
electron microscopy. Overall architecture of calcium release units is similar in 
control myocardium and in myocardium overexpressing junctin by 5-10-fold. In 
both myocardia, junctional SR cisternae are closely associated with exterior 
membranes (plasmalemma and transverse tubules). The cisternae are flat; they 
contain a string of calsequestrin beads and are lined by a row of feet, or RyRs, 
on the side facing the exterior membranes. T tubule surface density, measured as 
the perimeter of T tubule profiles v area of section, is the same in transgenic 
and control myocardia (305 v 289 nm/nm(2)). Three changes affecting the 
junctional SR architecture are apparent in the myocardium overexpressing 
junctin. One is a more tightly zippered appearance of the junctional SR 
cisternae. The width of the junctional SR is narrower and less variable in 
overexpressing than in control myocardium and the calsequestrin content is more 
compact. A second change is the extension of zippered junctional SR domains to 
non-junctional regions, which we term "frustrated" junctional SR. A third change 
is an increase in the extent of association between SR and T tubules. In junctin 
overexpressing myocardium junctional SR cisternae cover approximately 45% of the 
surface of all T tubule profiles, while in control myocardium the coverage 
approximately 30%. Junctional associations between SR and T tubules are 
increased in size. We conclude that the increase in junctin expression affects 
the packing of calsequestrin in the junctional SR and facilitates the 
association of SR and T tubules.