Mutations in Hsp40 co-chaperone change the unique canonical inter-domain interactions stimulating LGMDD1 myopathy.

Unlabelled: Limb-girdle muscular dystrophy D1 (LGMDD1) is a rare, dominantly inherited neuromuscular disorder caused by mutations in the HSP40 co-chaperone DNAJB6, primarily in the GF or J-domains. Currently, no treatments are available, and a challenge in understanding the disease is identifying a specific client protein for DNAJB6 in skeletal muscle. Our previous research indicated that LGMDD1 GF domain mutants in Sis1 exhibit substrate-specific effects, influenced by HSP70 activity.

Reconstitution of Arp2/3-Nucleated Actin Assembly with CP, V-1 and CARMIL.

Actin polymerization is often associated with membrane proteins containing capping-protein-interacting (CPI) motifs, such as CARMIL, CD2AP, and WASHCAP/Fam21. CPI motifs bind directly to actin capping protein (CP), and this interaction weakens the binding of CP to barbed ends of actin filaments, lessening the ability of CP to functionally cap those ends. The protein V-1 / myotrophin binds to the F-actin binding site on CP and sterically blocks CP from binding barbed ends.