membrane protein ectodomain proteolysis

Definition

Target type: biologicalprocess

The proteolytic cleavage of transmembrane proteins and release of their ectodomain (extracellular domain). [GOC:jl, http://www.copewithcytokines.de/]

Membrane protein ectodomain proteolysis is a crucial process in cellular signaling, development, and homeostasis. It involves the cleavage of the extracellular domain (ectodomain) of transmembrane proteins by specific proteases, often referred to as sheddases.

This process typically occurs at the cell surface, where the ectodomain is exposed to the extracellular environment. The shedding event releases the soluble ectodomain, which can then act as a signaling molecule or ligand. The remaining membrane-bound fragment, known as the "stub" or "cytoplasmic tail", can also undergo further modifications and participate in signaling pathways.

Here's a detailed breakdown of the process:

1. **Protease Recognition and Binding:** The first step involves the recognition and binding of the target transmembrane protein by a specific protease. Sheddases, such as ADAM (a disintegrin and metalloproteinase) and MMP (matrix metalloproteinase) families, are known for their role in ectodomain shedding. These proteases possess specific cleavage sites within the ectodomain, often located close to the transmembrane domain.

2. **Cleavage Event:** Once bound, the protease cleaves the target protein at the designated site, releasing the ectodomain from the cell surface. This cleavage event requires the protease to be active, which can be regulated by various factors like extracellular stimuli, cell signaling pathways, and post-translational modifications.

3. **Release of Soluble Ectodomain:** The cleaved ectodomain, now a soluble protein fragment, can be released into the extracellular space. This release allows the ectodomain to travel to distant targets and participate in various biological functions.

4. **Fate of the Membrane-Bound Stub:** The remaining transmembrane stub can also undergo further modifications, such as phosphorylation or ubiquitination. This may alter its interaction with other cellular components and influence downstream signaling pathways.

Ectodomain proteolysis is a tightly regulated process with numerous implications for cellular function. Its dysregulation can contribute to the development of various diseases, including cancer, Alzheimer's disease, and cardiovascular diseases.

The shedding process is influenced by several factors, including:

* **Cellular Context:** Different cell types express varying levels and types of sheddases, resulting in cell-specific patterns of ectodomain shedding.
* **Extracellular Stimuli:** Various stimuli, such as growth factors, cytokines, and hormones, can trigger ectodomain shedding by activating specific signaling pathways that regulate sheddase activity.
* **Post-Translational Modifications:** Modifications like phosphorylation or glycosylation can influence the susceptibility of target proteins to proteolytic cleavage.

In summary, ectodomain proteolysis is a dynamic and essential process that contributes to diverse biological functions, ranging from cell signaling to immune responses and development. The shedding event plays a critical role in modulating cellular behavior and communication, highlighting its importance in maintaining normal physiological function.'
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Proteins (19)

Compounds (982)