Related Experiment Video

Updated: Jun 7, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

TAM receptors and the clearance of apoptotic cells

Greg Lemke1, Tal Burstyn-Cohen

  • 1The Salk Institute, La Jolla, California 92037, USA. lemke@salk.edu

Annals of the New York Academy of Sciences
|October 21, 2010
PubMed

Insights

The Tyro3, Axl, and Mer (TAM) receptor system is crucial for clearing apoptotic cells, especially those signaling via phosphatidylserine. Deficiencies in TAM signaling are linked to retinal dystrophies and autoimmune diseases.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • The Tyro3, Axl, and Mer (TAM) receptor tyrosine kinases and their ligands Gas6 and Protein S are essential for efficient phagocytosis of apoptotic cells.
  • This system is vital in mature immune, nervous, and reproductive systems.

Purpose of the Study:

  • To elucidate the role of the TAM receptor-ligand system in apoptotic cell clearance.
  • To investigate the involvement of TAM signaling in phosphatidylserine-triggered phagocytosis.
  • To explore the connection between TAM deficiencies and human diseases.

Main Methods:

  • Genetic analyses in mice, rats, and humans.
  • Investigation of phagocytic signaling pathways.

Main Results:

  • The TAM system is critical for optimal phagocytosis of apoptotic cells, particularly those displaying the "eat-me" signal phosphatidylserine.
  • Deficiencies in TAM signaling are associated with human retinal dystrophies.
  • Impaired TAM signaling may contribute to autoimmune diseases such as lupus.

Conclusions:

  • The TAM receptor-ligand system is a key regulator of efferocytosis, especially in response to phosphatidylserine.
  • Dysfunction in TAM signaling has significant implications for human health, contributing to retinal dystrophies and autoimmune disorders.
  • The TAM system acts as a signaling hub, integrating with other phagocytic networks like scavenger receptors and integrins.

More Related Videos

Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages06:47

Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages

Published on: May 24, 2019

Quantification of Efferocytosis by Single-cell Fluorescence Microscopy06:15

Quantification of Efferocytosis by Single-cell Fluorescence Microscopy

Published on: August 18, 2018

Related Concept Videos

Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...