P8: The functional role of ahnak in skeletal muscle fibers in an ahnak knock-out mouse model
Ingo Morano and Hannelore Haase
Summary
Ahnak is a recently identified still poorly understood muscle phosphoprotein. Recently, we demonstrated that ahnak is associated with actin and inhibits the dihydropyridine-sensitive L-type Ca2+current via binding to its regulatory beta subunit in cardiac muscle. Therefore, ahnak regulates both excitation-contraction coupling, as well as the structural integrity of the cardiomyocyte. However, the functional and pathophysiological role of ahnak in skeletal muscle is unknown. The transmembrane protein dysferlin seems to anchor ahnak to the sarcolemma, thus providing a membrane-stabilizing dysferlin-ahnak-actin complex. Dysferlin deficiency is associated with limb girdle musclular dystrophy 2B (LGMD2B) and Miyoshi myopathy; however, the mechanisms of these diseases are not yet understood. We will investigate the hypothesis that the dysferlinopathies are associated with ahnak translocation and/or depressed expression.
A schematic of ahnak complexes in muscle is shown. Ahnak/ahnak2 can be anchored to the sarcolemma by the transmembrane protein dysferlin (left) or via the ß-subunit of the L-type Ca2+ channel (DHPR) (right), thereby linking the actin cytoskeleton to the plasma membrane. Ahnak is also a constituent of enlargeosomes luminal aspect.
