Nanodomain Signaling Controls Muscle Function

In the last years, significant progress in the excitation-contraction coupling (ECC) field has produced major new and exciting advances. These include insights into the importance of protein-protein allosteric interactions, surface/organelle ion homeostasis in health and disease and innovative leveraging of this new knowledge toward therapeutic strategies to address ECC-associated diseases in both skeletal and cardiac muscle. It has also emerged that signaling in nanometer scale domains (nanodomains) are critical regulators of not only the very first and determinative steps in muscle acti­va­tion (ECC), but also the resulting muscle function, memory and both adaptive and pathological remodeling. This is true for striated muscle types (skeletal and cardiac), the traditional foci of this GRC, but also for smooth muscle. We will re-introduce smooth muscle to this 2023 GRC, at a modest level for specific reasons. All 3 muscle types have similar ECC nanodomains, containing many of the same proteins, but the way they transduce ECC is quite different. Comparative discussion of how these 3 muscle types have become differentially specialized, using similar protein nanodomains will greatly inform all three fields.

The 2023 Muscle ECC GRC sessions will discuss new advances that span from the level of structure-function of individual proteins (e.g. the L-type Ca channel (LTCC) and ryanodine receptor (RyR)) and their nanodomain partners, to how these influence the integrated muscle, heart and vessel function in both health and diseases which afflict millions of people. Specific goals are: Goal 1: Assemble top-notch scientist-speakers and participants to share new breakthroughs in know­ledge, to stimulate and participate in deep and broad discussions that span from molecular mechanisms to integrated physiology and pathophysiology in muscle. This will enhance understanding and stimulate new discoveries related to the science of and therapeutic strategies for skeletal, cardiac and smooth muscle-related diseases. Goal 2: Increase the visibility and leadership of junior ECC ESIs (students, postdoctoral fellows & early assistant professors) and inspire/motivate their research careers to new highs by providing an interactive informal forum in which to present their work and network with each other as well as established ECC leaders. These overarching objectives will be met through, 1) an exciting scientific program focused on cutting-edge research presented by both established and new investigators, 2) incorporation of innovative elements like “Poster Preview Sessions” and “Late-Breaking Topic” poster talks to highlight late-breaking developments, 3) integration of ESI “questions first”, poster talks and ESI discussion co-leader roles at the GRC and 4) robust engagement with the preceding GRS.