Anchoring skeletal muscle development and disease: the role of ankyrin repeat domain containing proteins in muscle physiology

Abstract

The ankyrin repeat is a protein module with high affinity for other ankyrin repeats based on strong Van der Waals forces. The resulting dimerization is unusually resistant to both mechanical forces and alkanization, making this module exceedingly useful for meeting the extraordinary demands of muscle physiology. Many aspects of muscle function are controlled by the superfamily ankyrin repeat domain containing proteins, including structural fixation of the contractile apparatus to the muscle membrane by ankyrins, the archetypical member of the family. Additionally, other ankyrin repeat domain containing proteins critically control the various differentiation steps during muscle development, with Notch and developmental stage-specific expression of the members of the Ankyrin repeat and SOCS box (ASB) containing family of proteins controlling compartment size and guiding the various steps of muscle specification. Also, adaptive responses in fully formed muscle require ankyrin repeat containing proteins, with Myotrophin/V-1 ankyrin repeat containing proteins controlling the induction of hypertrophic responses following excessive mechanical load, and muscle ankyrin repeat proteins (MARPs) acting as protective mechanisms of last resort following extreme demands on muscle tissue. Knowledge on mechanisms governing the ordered expression of the various members of superfamily of ankyrin repeat domain containing proteins may prove exceedingly useful for developing novel rational therapy for cardiac disease and muscle dystrophies.

RAI14 (retinoic acid induced protein 14) is an F-actin regulator

“…It has three ankyrin repeat domains near its NH 2 -terminus. An ankyrin repeat is a 33-residue motif composed of two α helices separated by loops, and these ankyrin domains are crucial to induce protein-protein interactions and signal transduction 13 - 15 . These findings thus illustrate that RAI14 has the ability to recruit multiple signaling and regulatory proteins to F-actin via its ankyrin repeat domains to regulate multiple cellular functions, in particular F-actin cytoskeleton dynamics.…”

Genome-Wide Association Study of Short-Acting β2-Agonists. A Novel Genome-Wide Significant Locus on Chromosome 2 near ASB3

“…Furthermore, mouse studies have suggested that this gene family may have a role in myoblast differentiation (28). Lastly, Ankyrin repeat-containing proteins control the induction of hypertrophic responses in muscle in response to loads (29). These muscle regulatory functions could potentially explain the effect on the acute BDR, which is highly dependent on airway muscle function.…”

Transcriptional Response of Bovine Monocyte-Derived Macrophages after the Infection with Different ArgentineanMycobacterium bovisIsolates

“…Ankyrins contain repeat domains that interact with other ankyrin repeats. These ankyrin interactions act in many diverse functions and include regulation of transcription, cell cycle, cell fate determination, cytoskeletal integrity, cellular mechanosensation, and endocytosis [24, 25]. TCDD-inducible poly (ADP-ribose) polymerase, TiPARP, is the last upregulated gene in this group.…”