The small GTPase RAB-35 facilitates the initiation of phagosome maturation and acts as a robustness factor for apoptotic cell clearance
Autor: | Zheng Zhou, Ryan Haley |
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Rok vydání: | 2019 |
Předmět: |
Phagocytosis
Apoptosis Endosomes Biology Phosphatidylinositols Biochemistry Apoptotic cell clearance 03 medical and health sciences 0302 clinical medicine Phagosomes Phagosome maturation Animals Small GTPase Caenorhabditis elegans Caenorhabditis elegans Proteins Receptor 030304 developmental biology Phagosome 0303 health sciences Brief Report fungi Cell Biology Cell biology rab GTP-Binding Proteins 030220 oncology & carcinogenesis Guanine nucleotide exchange factor Rab Lysosomes |
Zdroj: | Small GTPases |
ISSN: | 2154-1256 2154-1248 |
Popis: | We recently identified the novel function of the small GTPase RAB-35 in apoptotic cell clearance in Caenorhabditis elegans, a process in which dying cells are engulfed and degraded inside phagosomes. We have found that RAB-35 functions in two separate steps of cell corpse clearance, cell corpse recognition and the initiation of phagosome maturation. During the latter process, RAB-35 facilitates the removal of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) from the membranes of nascent phagosomes and the simultaneous production of phosphatidylinositol-3-P (PI(3)P) on these same membranes, a process that we have coined the PI(4,5)P(2) to PI(3)P shift. RAB-35 also promotes the recruitment of the small GTPase RAB-5 to the phagosomal surface. During these processes, the activity of RAB-35 is controlled by the candidate GTPase-activating protein (GAP) TBC-10 and the candidate guanine nucleotide exchange factor (GEF) FLCN-1. Overall, RAB-35 leads a third pathway during cell corpse clearance that functions in parallel to the two known pathways, one led by the phagocytic receptor CED-1 and the other led by the CED-10/Rac1 GTPase. Here, we further report that RAB-35 acts as a robustness factor that maintains the clearance activity and embryonic viability under conditions of heat stress. Moreover, we obtained additional evidence suggesting that RAB-35 acts upstream of RAB-5 and RAB-7. To establish a precise temporal pattern for its own dissociation from phagosomal surfaces, RAB-35 controls the removal of its own GAP. We propose that RAB-35 defines a largely unexplored initial phase of phagosome maturation. |
Databáze: | OpenAIRE |
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