Gain-of-Function Dynamin-2 Mutations Linked to Centronuclear Myopathy Impair Ca²⁺-Induced Exocytosis in Human Myoblasts.

ABSTRACT: Gain-of-function mutations of dynamin-2, a mechano-GTPase that remodels membrane and actin filaments, cause centronuclear myopathy (CNM), a congenital disease that mainly affects skeletal muscle tissue. Among these mutations, the variants p.A618T and p.S619L lead to a gain of function and cause a severe neonatal phenotype. By using total internal reflection fluorescence microscopy (TIRFM) in immortalized human myoblasts expressing the pH-sensitive fluorescent protein (pHluorin) fused to the insulin-responsive aminopeptidase IRAP as a reporter of the GLUT4 vesicle trafficking, we measured single pHluorin signals to investigate how p.A618T and p.S619L mutations influence exocytosis. We show here that both dynamin-2 mutations significantly reduced the number and durations of pHluorin signals

SUBMITTER: Bayones L 

PROVIDER: S-EPMC9499313 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature