The Transitional Junction: A New Functional Subcellular Domain at the Intercalated Disc

Abstract

We define here a previously unrecognized structural element close to the heart muscle plasma membrane at the intercalated disc where the myofibrils lead into the adherens junction. At this location, the plasma membrane is extensively folded. Immunofluorescence and immunogold electron microscopy reveal a spectrin-rich domain at the apex of the folds. These domains occur at the axial level of what would be the final Z-disc of the terminal sarcomere in the myofibril, although there is no Z-disc-like structure there. However, a sharp transitional boundary lies between the myofibrillar I-band and intercalated disc thin filaments, identifiable by the presence of Z-disc proteins, ␣-actinin, and N-terminal titin. This allows for the usual elastic positioning of the A-band in the final sarcomere, whereas the transduction of the contractile force normally associated with the Z-disc is transferred to the adherens junctions at the plasma membrane. The axial conjunction of the transitional junction with the spectrin-rich domains suggests a mechanism for direct communication between intercalated disc and contractile apparatus. In particular, it provides a means for sarcomeres to be added to the ends of the cells during growth. This is of particular relevance to understanding myocyte elongation in dilated cardiomyopathy.

Cardiomyopathy in α-Kinase 3 (ALPK3)–Deficient Mice

“…The relatively mild cytoarchitectural lesions affecting myofibrils and intercalated discs that we observed in Alpk3-deficient mice have not been previously reported. Intercalated discs are important in the mechanical coupling and chemical communication between cardiomyocytes, 4 and our findings strongly suggest that ALPK3 is involved in the formation of these highly organized structures. Intercalated discs play a central role in establishing the proper alignment of myofibrils and in maintaining the overall structure and mechanical efficiency of cardiomyocytes, and it is known that abnormalities in cardiomyocyte cytoarchitecture can impair efficient energy transfer and contractile force production.…”

Biophysics of Titin in Cardiac Health and Disease

“…Interestingly, a recently-defined subcellular structure called the transitional junction connects myofilaments (including titin) and the intercalated disk [35], which may offer insights regarding how the T16I mutation in titin leads to a disease phenotype that mimics those often associated with desmosomal mutations.…”

Intercalated discs: multiple proteins perform multiple functions in non-failing and failing human hearts

“…2). More recently, a new region, the "transitional junction" was described (Bennett et al 2006) at the perimeter of fascia adherens. It is considered to be a spectrin-rich site where sarcomeres can be added to myofibrils during growth (hypertrophy) and development.…”

“…A recent report by Bennett et al (2006) defined a new functional subcellular domain at the intercalated disc. Where the myofibrils insert at the fasica adherens, the plasma membrane is extensively folded and convoluted.…”