slit diaphragm

Definition

Target type: cellularcomponent

A specialized cell-cell junction found between the interdigitating foot processes of the glomerular epithelium (the podocytes) in the vertebrate kidney, which is adapted for facilitating glomerular filtration. [GOC:mtg_kidney_jan10, GOC:rph, PMID:12386277, PMID:15994232, PMID:18971929, PMID:19478094]

The slit diaphragm (SD) is a specialized cell-cell junction found exclusively between podocytes, the epithelial cells that wrap around capillaries in the glomerulus of the kidney. It plays a critical role in filtering blood and maintaining the integrity of the glomerular filtration barrier. The SD is composed of a complex network of transmembrane proteins and associated cytoplasmic proteins that interact to form a highly selective barrier. The structure of the SD can be broadly divided into three main components:

**1. Transmembrane proteins:** These proteins span the plasma membrane of adjacent podocytes and form the core structure of the SD. The key transmembrane proteins include:

* **Nephrin:** A type I transmembrane protein that acts as the central scaffold for SD assembly. Nephrin molecules from adjacent podocytes interact via their extracellular domains to form a zipper-like structure.
* **Podocin:** A transmembrane protein that interacts with nephrin and is essential for proper SD function. It contributes to the stability and curvature of the SD.
* **CD2AP:** A cytoplasmic adaptor protein that links nephrin to the actin cytoskeleton, providing structural support and regulating SD assembly.
* **P-cadherin:** A calcium-dependent cell adhesion molecule that contributes to the adhesive properties of the SD and interacts with nephrin.
* **FAT1:** A large transmembrane protein with a large extracellular domain, contributing to the organization and stability of the SD.

**2. Cytoplasmic proteins:** These proteins are located on the cytoplasmic side of the plasma membrane and interact with transmembrane proteins to regulate SD function. Important cytoplasmic proteins include:

* **Nck:** An adaptor protein that binds to nephrin and recruits other signaling molecules to the SD.
* **ZO-1:** A tight junction protein that interacts with the cytoplasmic tails of nephrin and CD2AP, contributing to the integrity and stability of the SD.
* **α-actinin-4:** An actin-binding protein that links the SD to the actin cytoskeleton.
* **Synaptopodin:** A protein that interacts with nephrin and podocin, contributing to the regulation of podocyte cytoskeletal dynamics.

**3. Extracellular matrix:** The space between the two podocytes, where the SD is located, is filled with a specialized extracellular matrix (ECM). This ECM contains a variety of molecules, including:

* **Heparan sulfate proteoglycans:** These molecules contribute to the selective permeability of the SD by interacting with specific proteins in the filtrate.
* **Collagen IV:** Provides structural support and helps maintain the integrity of the SD.
* **Laminin:** A component of the basement membrane that interacts with both the SD and the podocyte cytoskeleton.

The SD is highly dynamic and undergoes constant remodeling in response to changes in filtration pressure and other physiological stimuli. Its complex structure and regulation ensure the efficient filtration of blood and the prevention of proteinuria, a hallmark of kidney disease. Disruptions in the assembly, function, or integrity of the SD can lead to various forms of glomerular disease, highlighting the importance of this specialized cell-cell junction for kidney health.'"

Proteins (2)

Compounds (4)