Related Experiment Video

Updated: May 15, 2026

Generation of Patient-Derived Podocytes from Skin Biopsies
08:52

Generation of Patient-Derived Podocytes from Skin Biopsies

Published on: May 26, 2023

mVps34 deletion in podocytes causes glomerulosclerosis by disrupting intracellular vesicle trafficking

Jianchun Chen1, Mystie X Chen, Agnes B Fogo

  • 1Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Journal of the American Society of Nephrology : JASN
|January 8, 2013
PubMed

Insights

The mammalian homologue of yeast vacuolar protein sorting defective 34 (mVps34) is essential for podocyte health. Loss of mVps34 in podocytes causes severe kidney disease and early death in mice.

Area of Science:

  • Nephrology
  • Cell Biology
  • Autophagy Research

Background:

  • Autophagy is crucial for podocyte integrity.
  • The role of mammalian vacuolar protein sorting defective 34 (mVps34) in podocytes remains unclear.

Purpose of the Study:

  • To investigate the function of mVps34 in podocyte biology.
  • To determine the consequences of podocyte-specific mVps34 deficiency.

Main Methods:

  • Generation of podocyte-specific mVps34-knockout (mVps34(pdKO)) mice.
  • Phenotypic analysis including growth, kidney function (proteinuria), and survival.
  • Histological examination (light and electron microscopy) of kidney tissues.
  • Biochemical analysis (immunoblotting and immunofluorescence) of glomerular and lysosomal markers.

Main Results:

  • mVps34(pdKO) mice exhibited growth retardation and premature death before 9 weeks of age.
  • Significant proteinuria, glomerulosclerosis, interstitial fibrosis, and podocyte vacuolization were observed.
  • Electron microscopy revealed enlarged vacuoles, increased autophagosomes, foot process effacement, and GBM abnormalities.
  • Elevated lysosomal (LAMP1, LAMP2) and autophagosomal (LC3-II/I) markers confirmed impaired autophagy and lysosomal dysfunction.

Conclusions:

  • mVps34 is indispensable for maintaining podocyte structure and function.
  • mVps34 plays a critical role in intracellular vesicle trafficking and cellular metabolism within podocytes.
  • Disruption of mVps34 leads to severe kidney pathology, highlighting its importance in preventing podocyte disease.

More Related Videos

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

Isolation of Glomeruli and In Vivo Labeling of Glomerular Cell Surface Proteins09:12

Isolation of Glomeruli and In Vivo Labeling of Glomerular Cell Surface Proteins

Published on: January 18, 2019

Related Concept Videos

Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
Overview of Secretory Vesicles01:33

Overview of Secretory Vesicles

Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...