regulation of engulfment of apoptotic cell

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of engulfment of apoptotic cell. [GO:kmv, GOC:TermGenie, PMID:19402756]

The regulation of engulfment of apoptotic cells, a critical process in tissue homeostasis, involves a complex interplay of signaling pathways, receptors, and intracellular mediators. It is essential for the timely and efficient removal of dying cells to prevent inflammation and maintain tissue integrity.

The process begins with the recognition of apoptotic cells by neighboring cells or professional phagocytes, such as macrophages. This recognition is mediated by a variety of "eat me" signals displayed on the surface of apoptotic cells, including phosphatidylserine (PS) exposure, which is normally located on the inner leaflet of the plasma membrane but flips to the outer leaflet during apoptosis. Other "eat me" signals include calreticulin, thrombospondin, and oxidized low-density lipoprotein (oxLDL).

These signals are detected by specific receptors on phagocytes. Among the most well-studied receptors are:

* **Phosphatidylserine receptors:** These include TIM-4, BAI1, and stabilin-2, which directly bind PS exposed on apoptotic cells.
* **Complement receptors:** Receptors like CR3 (CD11b/CD18) recognize complement proteins that bind to apoptotic cells.
* **Scavenger receptors:** Receptors like SR-A and CD36 recognize various ligands, including oxLDL, that can be displayed on apoptotic cells.
* **Other receptors:** Additional receptors, like CD14, lectins, and integrins, may contribute to apoptotic cell recognition.

Upon receptor engagement, intracellular signaling pathways are activated, leading to the recruitment and activation of downstream proteins. These pathways include:

* **PI3K/Akt pathway:** This pathway promotes cell survival and phagocytic activity, contributing to the efficient engulfment of apoptotic cells.
* **Rho GTPase pathway:** This pathway regulates cytoskeletal rearrangements and membrane protrusions necessary for phagocytosis.
* **Rac1 pathway:** This pathway controls actin polymerization and the formation of phagocytic cups that engulf apoptotic cells.
* **Small GTPases:** Other small GTPases, like Cdc42, also contribute to cytoskeletal rearrangements.

The activation of these signaling pathways ultimately leads to the engulfment of apoptotic cells. Phagocytes extend pseudopodia, membrane protrusions, that enclose the apoptotic cell, forming a phagocytic cup. The apoptotic cell is then internalized within a phagosome, a membrane-bound vesicle.

Once inside the phagocyte, the apoptotic cell is degraded by lysosomal enzymes. This degradation process ensures the safe removal of the apoptotic cell's components and prevents the release of potentially damaging cellular contents.

The regulation of engulfment is tightly controlled, ensuring proper clearance of apoptotic cells and preventing the development of autoimmune diseases or inflammation. Dysregulation of engulfment can contribute to various pathological conditions, including cancer, neurodegenerative diseases, and autoimmune disorders.

Therefore, understanding the intricate mechanisms involved in apoptotic cell engulfment is crucial for developing new therapeutic strategies for treating these conditions.'
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Proteins (1)

Compounds (60)