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PMID:24759100
| Citation |
Nam, TS, Park, KH, Shawl, AI, Kim, BJ, Han, MK, Kim, Y, Moss, J and Kim, UH (2014) Critical role for NAD glycohydrolase in regulation of erythropoiesis by hematopoietic stem cells through control of intracellular NAD content. J. Biol. Chem. 289:16362-73 |
|---|---|
| Abstract |
NAD glycohydrolases (NADases) catalyze the hydrolysis of NAD to ADP-ribose and nicotinamide. Although many members of the NADase family, including ADP-ribosyltransferases, have been cloned and characterized, the structure and function of NADases with pure hydrolytic activity remain to be elucidated. Here, we report the structural and functional characterization of a novel NADase from rabbit reticulocytes. The novel NADase is a glycosylated, glycosylphosphatidylinositol-anchored cell surface protein exclusively expressed in reticulocytes. shRNA-mediated knockdown of the NADase in bone marrow cells resulted in a reduction of erythroid colony formation and an increase in NAD level. Furthermore, treatment of bone marrow cells with NAD, nicotinamide, or nicotinamide riboside, which induce an increase in NAD content, resulted in a significant decrease in erythroid progenitors. These results indicate that the novel NADase may play a critical role in regulating erythropoiesis of hematopoietic stem cells by modulating intracellular NAD. |
| Links |
PubMed PMC4047404 Online version:10.1074/jbc.M114.560359 |
| Keywords |
Amino Acid Sequence; Animals; Base Sequence; Blotting, Western; DNA, Complementary; Erythropoiesis; Glycosylation; HEK293 Cells; Hematopoietic Stem Cells/metabolism; Humans; Microscopy, Confocal; Molecular Sequence Data; Mutagenesis, Site-Directed; NAD/metabolism; NAD+ Nucleosidase/chemistry; NAD+ Nucleosidase/genetics; NAD+ Nucleosidase/metabolism; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; Structure-Activity Relationship |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0019677: NAD catabolic process |
ECO:0000314: |
P |
Figure 6, panel A shows that the wild type NADase has a high specific NAD glucohydrolase activity. |
complete | ||||
| GO:0005886: plasma membrane |
ECO:0000314: |
C |
Figure 4A shows GFP-tagged NADase localizes to the plasma membrane |
complete | ||||
Notes
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