phagosome-lysosome fusion
Definition
Target type: biologicalprocess
The creation of a phagolysosome from a phagosome and a lysosome. [GOC:kmv, GOC:tb]
Phagosome-lysosome fusion is a critical process in eukaryotic cells for the degradation and removal of cellular debris, pathogens, and other unwanted materials. It involves a complex series of steps orchestrated by a network of proteins and signaling pathways.
1. **Phagosome Formation:** The process begins with the engulfment of a target by a phagocytic cell, such as a macrophage or neutrophil. The cell membrane invaginates around the target, forming a vesicle known as a phagosome. This engulfment is mediated by receptors on the cell surface that recognize and bind to the target.
2. **Phagosome Maturation:** Once formed, the phagosome undergoes a series of maturation steps that prime it for fusion with the lysosome. This maturation involves changes in the phagosome membrane composition, including the recruitment of specific proteins and lipids. These changes are essential for ensuring proper interaction with the lysosome.
3. **Recruitment of Rab GTPases:** Rab GTPases are small GTP-binding proteins that play critical roles in vesicle trafficking and fusion. Different Rab proteins are associated with specific cellular compartments, and their activation is essential for directing the phagosome to the lysosome. Rab5, Rab7, and Rab9 are key Rab GTPases involved in phagosome maturation and fusion.
4. **Tethering and Docking:** After Rab GTPase activation, the phagosome and lysosome are brought into close proximity through a tethering process mediated by tethering proteins. These proteins act as molecular bridges, helping to align the two organelles for fusion.
5. **Fusion:** The final step in phagosome-lysosome fusion involves the merging of the phagosome and lysosome membranes. This fusion event is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. SNARE proteins on the phagosome and lysosome membranes interact with each other, bringing the two membranes together and facilitating their fusion.
6. **Hydrolytic Degradation:** Once the phagosome and lysosome have fused, the contents of the phagosome are exposed to the hydrolytic enzymes within the lysosome. These enzymes degrade the engulfed material, breaking it down into smaller molecules that can be recycled or excreted from the cell.
The entire process of phagosome-lysosome fusion is tightly regulated and involves the interplay of numerous proteins and signaling pathways. Disruptions in this process can lead to various cellular defects and diseases. For example, defects in phagosome-lysosome fusion can contribute to impaired immune function, increased susceptibility to infections, and accumulation of cellular debris, which can damage cells and tissues.'
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Proteins (3)
| Protein | Definition | Taxonomy |
|---|---|---|
| 1-phosphatidylinositol 3-phosphate 5-kinase | A 1-phosphatidylinositol 3-phosphate 5-kinase that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y2I7] | Homo sapiens (human) |
| Ras-related protein Rab-7a | A Ras-related protein Rab-7a that is encoded in the genome of human. [PRO:DNx, UniProtKB:P51149] | Homo sapiens (human) |
| Phospholipase A2 group V | A phospholipase A2 group V that is encoded in the genome of human. [PRO:DNx, UniProtKB:P39877] | Homo sapiens (human) |
Compounds (11)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| 3-octylthio-1,1,1-trifluoro-2-propanone | 3-octylthio-1,1,1-trifluoro-2-propanone: a pesticide synergist; inhibits juvenile hormone esterase | ||
| varespladib | aromatic ether; benzenes; dicarboxylic acid monoamide; indoles; monocarboxylic acid; primary carboxamide | anti-inflammatory drug; antidote; EC 3.1.1.4 (phospholipase A2) inhibitor | |
| 2-[[benzamido(sulfanylidene)methyl]amino]-5,5-dimethyl-4,7-dihydrothieno[2,3-c]pyran-3-carboxylic acid | CID1067700: a pan-GTPase inhibitor; structure in first source | thienopyran | |
| vacuolin-1 | vacuolin-1: inhibits Ca2-dependent lysosomal exocytosis | ||
| ym 26734 | YM 26734: inhibits group II phospholipase A2; structure given in first source | ||
| indoxam | indoxam: structure in first source | ||
| ym 201636 | 6-amino-N-(3-(4-(4-morpholinyl)pyrido(3',2'-4,5)furo(3,2-d)pyrimidin-2-yl)phenyl)-3-pyridinecarboxamide: an antiviral agent; structure in first source | aromatic amide | |
| apilimod | |||
| apy0201 | APY0201: a small molecular IL-12/23 inhibitor with pyrazolo[1,5-a]pyrimidine core; structure in first source | ||
| guanosine diphosphate | Guanosine Diphosphate: A guanine nucleotide containing two phosphate groups esterified to the sugar moiety. | guanosine 5'-phosphate; purine ribonucleoside 5'-diphosphate | Escherichia coli metabolite; mouse metabolite; uncoupling protein inhibitor |
| guanosine triphosphate | Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety. | guanosine 5'-phosphate; purine ribonucleoside 5'-triphosphate | Escherichia coli metabolite; mouse metabolite; uncoupling protein inhibitor |