Class III Phosphatidylinositol-3 Kinase/Vacuolar Protein Sorting 34 in Cardiovascular Health and Disease

Yuanjun Shen1,2, Jason P Gleghorn3,4

  • 1Departments of Biomedical Engineering, University of Delaware, Newark, DE, USA. yjshen@udel.edu.

Insights

Vacuolar protein sorting 34 (VPS34), a key enzyme in cardiovascular health, is crucial for cell survival and thrombosis. Understanding VPS34

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Phosphatidylinositol-3 kinases (PI3Ks) are vital in cardiovascular health and disease.
  • Vacuolar protein sorting 34 (VPS34), the sole Class III PI3K, significantly impacts cardiovascular disease (CVD) progression.
  • VPS34 regulates phosphatidylinositol 3-phosphate production, influencing mTOR signaling, autophagy, and endocytosis.

Purpose of the Study:

  • To review current knowledge on VPS34 function and regulation in cardiovascular health and disease.
  • To highlight recent advancements in understanding VPS34's role in the cardiovascular system.
  • To discuss the therapeutic potential of VPS34 inhibitors for treating CVDs.

Main Methods:

  • Literature review of scientific articles on VPS34 and cardiovascular systems.
  • Analysis of VPS34's molecular functions, including its role in cell proliferation, survival, and thrombosis.
  • Examination of current research on VPS34 inhibitors and their clinical applications.

Main Results:

  • VPS34 is essential for vascular smooth muscle cell and cardiomyocyte proliferation and survival.
  • VPS34 plays a critical role in the formation of thrombosis.
  • VPS34's involvement in autophagy and endocytosis is crucial for cardiovascular homeostasis.

Conclusions:

  • VPS34 is a key regulator of cardiovascular function and a potential therapeutic target for CVDs.
  • Further research into VPS34 regulation and inhibition is warranted for developing novel CVD treatments.
  • Targeting VPS34 may offer a promising strategy for managing cardiovascular diseases.

Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.4K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
11.8K
ATP Driven Pumps III: V-type Pumps01:30

ATP Driven Pumps III: V-type Pumps

V-type pumps are ATP-driven pumps found in the vacuolar membranes of plants, yeast, endosomal and lysosomal membranes of animal cells, plasma membranes of a few specialized eukaryotic cells, and some prokaryotes. They are also known as the V1Vo-ATPase, that couple ATP hydrolysis to transport protons against a concentration gradient.
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...
3.5K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
2.3K
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...
3.4K
The Early Endosome: Endocytosis of Transferrin01:28

The Early Endosome: Endocytosis of Transferrin

Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
3.2K