Investigation of satellite cell behavior and extracellular vesicles in centronuclear myopathy

• Grant number: 17/07376-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 21, 2017
• End date: August 20, 2018
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mariz Vainzof
• Grantee: Camila de Freitas Almeida
• Supervisor: Marc Bitoun
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Université Pierre et Marie Curie (Paris 6), France
• Associated to the scholarship: 15/18914-4 - Study of the regenerative potential of satellite cells in centronuclear myopathy and myogenic capacity of its released microvesicles, BP.DR

Abstract

Centronuclear myopathies are genetic disorders that cause muscle wasting and weakness. Mutations in different genes have been identified, with different inheritance patterns. One of them is DNM2, which encodes a large GTPase responsible for the release of nascent vesicles during endocytosis, among other functions related to intracellular membrane trafficking. Muscles from CNM patients are characterized by the presence of central nuclei in the muscle fiber. Central nuclei are present during embryonic development and adult regeneration, however, in CNMs, no signs of muscle degeneration are found. Muscle has a special capability to regenerate thanks to the action of muscle-specific stem cells, named satellite cells. Still, in neuromuscular disorders, these cells are frequently affected by the primary mutation and can have their functions impaired.Extracellular vesicles (EVs) are released by cells both in normal and disease conditions, charged with many molecules, serving as molecular messengers between cells. Recent publications show a participation of EVs in neuromuscular disorders. Thus, in this project we will study satellite cells and EVs obtained from the mouse model for CNM with DNM2 mutation in order to check the role of DNM2 protein in muscle regeneration and cell communication, aiming the identification of possible targets for therapies.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

F. ALMEIDA, CAMILA; BITOUN, MARC; VAINZOF, MARIZ. Satellite cells deficiency and defective regeneration in dynamin 2-related centronuclear myopathy. FASEB JOURNAL, v. 35, n. 4, APR 2021. (17/07376-7, 13/08028-1, 15/18914-4)