CR3 ruffles FcγR's claim over phagocytic cups
1Geriatric Research Education and Clinical Center, Veterans Greater Los Angeles HealthCare System, Los Angeles, California, USA; Departments of Neurology and Medicine, University of California, Los Angeles, Los Angeles, California, USA.
The Journal of Biological Chemistry
|May 21, 2021
Summary
New imaging reveals complement receptor CR3-mediated phagocytosis occurs via sinking, while antibody-mediated phagocytosis uses cup formation. This challenges dogma, showing CR3
Area of Science:
- Immunology
- Cell Biology
Background:
- Phagocytosis is crucial for immunity and development, but its dynamic mechanisms and signaling pathways remain incompletely understood.
- Previous understanding relied on static images, limiting visualization of rapid phagocytic events.
Purpose of the Study:
- To visualize and elucidate the distinct mechanisms and interplay of different phagocytosis modes in real-time.
- To investigate the role of complement receptor CR3 in various phagocytic processes.
Main Methods:
- Utilized advanced time-lapse 3D imaging to capture the engulfment of erythrocytes by macrophages.
- Investigated phagocytosis mediated by complement receptor CR3 and antibody receptors.
Main Results:
- Confirmed complement receptor CR3-mediated phagocytosis occurs via a "sinking" mechanism.
- Demonstrated antibody-mediated phagocytosis proceeds through "cup formation."
- Showed phagocytic cup formation is not exclusive to antibody receptors and CR3 plays a complex regulatory role, with compensatory upregulation observed upon antibody-mediated phagocytosis inhibition.
Conclusions:
- Provides the first dynamic visualization of distinct phagocytosis mechanisms.
- Challenges established dogma regarding phagocytic cup formation and CR3 function.
- Reveals intricate interactions between different phagocytic pathways, advancing fundamental understanding of cellular engulfment.
Related Concept Videos
Phagocytosis
7.0K
Cells pull particles inward and engulf them in spherical vesicles in an energy-requiring process called endocytosis. Phagocytosis ("cellular eating") is one of three major types of endocytosis. Cells use phagocytosis to take in large objects, such as other cells (or their debris), bacteria, and even viruses.
The objective of phagocytosis is often destruction. Cells use phagocytosis to eliminate unwelcome visitors, like pathogens (e.g., viruses and bacteria). Many immune system cells,...
The objective of phagocytosis is often destruction. Cells use phagocytosis to eliminate unwelcome visitors, like pathogens (e.g., viruses and bacteria). Many immune system cells,...
7.0K
Phagocytosis
89.0K
Cells pull particles inward and engulf them in spherical vesicles in an energy-requiring process called endocytosis. Phagocytosis (“cellular eating”) is one of three major types of endocytosis. Cells use phagocytosis to take in large objects—such as other cells (or their debris), bacteria, and even viruses.
89.0K
Rab Proteins
4.5K
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...
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...
4.5K
Recycling Endosomes and Transcytosis
3.1K
The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
3.1K
Rab Cascades
3.0K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
3.0K
COP Coated Vesicles
14.4K
Membrane-enclosed structures called vesicles transport proteins and lipids across the cell. The vesicles derive their cargo from the plasma membrane, Golgi, ER, or endosome. Coated vesicles are spherical, protein-coated carriers with a 50–100 nm diameter that mediate bidirectional transport between the ER and the Golgi. The distribution of proteins between the ER and Golgi complex is dynamic and is maintained by different coated vesicles. Their formation is driven by the assembly of...
14.4K


