Critical role for NAD glycohydrolase in regulation of erythropoiesis by hematopoietic stem cells through control of intracellular NAD content.
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.
From the Department of Biochemistry, National Creative Research Laboratory for Ca Signaling Network, and.
Tae-Sik
TS
Nam
From the Department of Biochemistry, National Creative Research Laboratory for Ca Signaling Network, and.
Kwang-Hyun
KH
Park
From the Department of Biochemistry, National Creative Research Laboratory for Ca Signaling Network, and.
Asif Iqbal
AI
Shawl
From the Department of Biochemistry, National Creative Research Laboratory for Ca Signaling Network, and.
Byung-Ju
BJ
Kim
Department of Microbiology, Chonbuk National University Medical School, Jeonju 561-182, Korea.
Myung-Kwan
MK
Han
Department of Biochemistry, School of Medicine, Wonkwang University, Iksan 570-749, Korea, and.
Youngho
Y
Kim
Cardiovascular and Pulmonary Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892.
Joel
J
Moss
From the Department of Biochemistry, National Creative Research Laboratory for Ca Signaling Network, and Institute of Cardiovascular Research, Chonbuk National University Medical School, Jeonju 561-182, Korea, uhkim@chonbuk.ac.kr.
Uh-Hyun
UH
Kim
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D018076:DNA, Complementary; D004920:Erythropoiesis; D006031:Glycosylation; D057809:HEK293 Cells; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009243:NAD / Q000378:metabolism*; D009244:NAD+ Nucleosidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship
D018076:DNA, Complementary; D009243:NAD; D009244:NAD+ Nucleosidase
CD38; Erythrocyte; Erythropoiesis; Hematopoietic Stem Cell; Intracellular NAD; NAD Glycohydrolase; Nicotinamide; Nicotinamide Adenine Dinucleotide (NAD); Reticulocytes