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Rab5c-mediated endocytic trafficking regulates hematopoietic stem and progenitor cell development via Notch and AKT signaling
- Source :
- PLoS Biology, PLoS Biology, Vol 18, Iss 4, p e3000696 (2020)
- Publication Year :
- 2019
-
Abstract
- It is well known that various developmental signals play diverse roles in hematopoietic stem and progenitor cell (HSPC) production; however, how these signaling pathways are orchestrated remains incompletely understood. Here, we report that Rab5c is essential for HSPC specification by endocytic trafficking of Notch and AKT signaling in zebrafish embryos. Rab5c deficiency leads to defects in HSPC production. Mechanistically, Rab5c regulates hemogenic endothelium (HE) specification by endocytic trafficking of Notch ligands and receptor. We further show that the interaction between Rab5c and Appl1 in the endosome is required for the survival of HE in the ventral wall of the dorsal aorta through AKT signaling. Interestingly, Rab5c overactivation can also lead to defects in HSPC production, which is attributed to excessive endolysosomal trafficking inducing Notch signaling defect. Taken together, our findings establish a previously unrecognized role of Rab5c-mediated endocytic trafficking in HSPC development and provide new insights into how spatiotemporal signals are orchestrated to accurately execute cell fate transition.<br />Cell-autonomous Notch signaling regulated by the membrane trafficking protein Rab5c plays an instructive role in hematopoietic stem and progenitor cell specification, while the AKT signaling seems to provide a permissive signal to maintain hemogenic endothelium survival.
- Subjects :
- 0301 basic medicine
Embryology
Embryo, Nonmammalian
Endocytic cycle
Immunostaining
Biochemistry
Animals, Genetically Modified
0302 clinical medicine
Cell Signaling
Biology (General)
Zebrafish
Hemogenic endothelium
Notch Signaling
Staining
Receptors, Notch
General Neuroscience
Gene Expression Regulation, Developmental
Eukaryota
Animal Models
Endocytosis
Cell biology
Experimental Organism Systems
Osteichthyes
Vertebrates
293T cells
Cell lines
Signal transduction
Cellular Structures and Organelles
General Agricultural and Biological Sciences
Biological cultures
Research Article
Signal Transduction
QH301-705.5
Endosome
Notch signaling pathway
Endosomes
Cell fate determination
Biology
Green Fluorescent Protein
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Model Organisms
Animals
Humans
Endothelium
Vesicles
Progenitor cell
Protein kinase B
rab5 GTP-Binding Proteins
General Immunology and Microbiology
Embryos
Organisms
Biology and Life Sciences
Proteins
Cell Biology
Zebrafish Proteins
Hematopoietic Stem Cells
Research and analysis methods
Luminescent Proteins
030104 developmental biology
HEK293 Cells
Fish
Specimen Preparation and Treatment
Fertilization
Animal Studies
T-Box Domain Proteins
Proto-Oncogene Proteins c-akt
030217 neurology & neurosurgery
Transcription Factors
Developmental Biology
Subjects
Details
- ISSN :
- 15457885
- Volume :
- 18
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS biology
- Accession number :
- edsair.doi.dedup.....4adc61cb4e6cae7288d6c08723a35f19