The importance of scaffolding proteins for heart cell function

Biophysical investigation of nesprin spectrin repeats: implications for cardiovascular cell function

Cardiomyopathy is a disease of the heart muscle. It can run in families and can affect more than one member of a family. The disease is caused by faulty genes carried in a person’s DNA. Dr Franca Fraternali and her colleagues at King’s College London, a BHF Centre of Research Excellence, are studying a family of giant structural proteins called nesprins. These are common proteins in the heart and act like an internal scaffold in heart cells ensuring they are strong enough to withstand the strain while beating. People who have genetic mutations causing faulty nesprins can develop a condition called dilated cardiomyopathy (DCM). In DCM the heart muscle wall is thin making it hard for the heart to pump blood around the body efficiently. Faulty nesprins are also found in people with Emery Dreifuss muscular dystrophy (EDMD). Nesprins are made up of Lego brick-like modules called spectrin repeats (SRs). Dr Fraternali thinks it could be disruption of the interactions between SRs and other proteins they bind to in cells that cause DCM and EDMD in some cases. She wants to analyse their role further through a biophysical investigation where the physical properties, like strength, of the molecules are measured. Dr Fraternali will further investigate the role of nesprins by comparing working nesprins with faulty ones. She will also be looking at a potential therapy for people who might have faulty nesprins causing DCM or EDMD. It is hoped this project will help answer key questions about the structural properties of nesprins to give us a better idea how genetic conditions such as DCM and EDMD are caused and hopefully lead to new therapies for DCM and EDMD.