Activation of SIRT1 promotes membrane resealing via cortactin

Naotoshi Iwahara1,2, Kuya Azekami1, Ryusuke Hosoda1

  • 1Department of Pharmacology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Scientific Reports
|September 12, 2022
PubMed

Insights

Resveratrol enhances muscle membrane repair by activating SIRT1, which promotes cytoskeletal reorganization. This mechanism involves cortactin, offering a potential therapeutic avenue for muscular dystrophies.

Area of Science:

  • Muscle physiology and cellular repair mechanisms.
  • Investigating therapeutic compounds for inherited myopathies.

Background:

  • Muscular dystrophies cause progressive muscle weakness, with limited treatment options.
  • Resveratrol, a SIRT1 activator, shows potential in ameliorating muscular function, but its mechanism is unclear.

Purpose of the Study:

  • To investigate the effects of resveratrol on muscle membrane resealing.
  • To elucidate the molecular mechanisms underlying resveratrol-mediated membrane repair.

Main Methods:

  • Utilized C2C12 cells and single muscle fibers from mice for membrane repair assays.
  • Examined the role of SIRT1, actin, and cortactin in resveratrol-induced membrane repair.
  • Investigated SIRT1's effect on cortactin deacetylation and F-actin interaction.

Main Results:

  • Resveratrol promoted membrane repair in C2C12 cells and ex vivo muscle fibers via SIRT1 activation.
  • Resveratrol enhanced actin accumulation at injury sites.
  • SIRT1 deacetylated cortactin, promoting its interaction with F-actin, crucial for cytoskeletal reorganization and repair.

Conclusions:

  • Resveratrol facilitates muscle membrane repair through the SIRT1/cortactin pathway.
  • Targeting the SIRT1/cortactin axis may offer a novel therapeutic strategy for muscular dystrophies.

Related Concept Videos

Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Cell Motility through Blebbing01:16

Cell Motility through Blebbing

Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
2.0K
Enlargement of the Plasma Membrane01:22

Enlargement of the Plasma Membrane

Cell division and enlargement are processes that require precise control. The control ensures that cell division cannot proceed unless the cell has grown to a specific size. A spherical, dividing cell requires an approximately 1.6X increase in its surface area to double its volume. The secretory pathway also has a significant role in cell membrane enlargement. Secretory vesicles that bud off from the Golgi apparatus and later fuse with the plasma membrane during exocytosis are a major source of...
2.0K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.8K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.9K