Localization of Plasma Membrane CD38 Is Domain Specific in Rat Hepatocyte

Khoo, Keng Meng; Chang, Chan Fong

doi:10.1006/abbi.1999.1526

Cited by 18 publications

(12 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are claims that the NAD glycohydrolase/ADP-ribosyl cyclase activity corresponds to the CD38 protein, which is present in many cells [2] . The existence of CD38 in the plasma membrane of hepatocytes has indeed been demonstrated by Khoo and Chang [5] . In liver cells, this protein shows a 10-fold higher specific activity in the sinusoidal membrane fraction than in the bile canalicular membrane fraction.…”

Section: Introductionmentioning

confidence: 60%

Transformation and action of extracellular NAD+ in perfused rat and mouse livers

Broetto-Biazon

Bracht

et al. 2008

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: Transformation and possible metabolic effects of extracellular NAD + were investigated in the livers of mice (Mus musculus; Swiss strain) and rats (Rattus novergicus; Holtzman and Wistar strains). Methods: The livers were perfused in an open system using oxygen-saturated Krebs/Henseleit-bicarbonate buffer (pH 7.4) as the perfusion fluid. The transformation of NAD + was monitored using high-performance liquid chromatography. Results: In the mouse liver, the single-pass metabolism of 100 µmol/L NAD + was almost complete; ADP-ribose and nicotinamide were the main products in the outflowing perfusate. In the livers of both Holtzman and Wistar rats, the main transformation products were ADP-ribose, uric acid and nicotinamide; significant amounts of inosine and AMP were also identified. On a weight basis, the transformation of NAD + was more efficient in the mouse liver. In the rat liver, 100 µmol/L NAD + transiently inhibited gluconeogenesis and oxygen uptake. Inhibition was followed by a transient stimulation. Inhibition was more pronounced in the Wistar strain and stimulation was more pronounced in the Holtzman strain. In the mouse liver, no clear effects on gluconeogenesis and oxygen uptake were found even at 500 µmol/L NAD + . Conclusion:It can be concluded that the functions of extracellular NAD + are species-dependent and that observations in one species are strictly valid for that species. Interspecies extrapolations should thus be made very carefully. Actually, even variants of the same species can demonstrate considerably different responses.

show abstract

Section: Introductionmentioning

confidence: 60%

Transformation and action of extracellular NAD+ in perfused rat and mouse livers

Broetto-Biazon

Bracht

et al. 2008

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…For example, it has been suggested that two extracellular cysteines in CD38 (Cys119 and Cys201 in human CD38 or Cys123 and Cys205 in mouse CD38) could form interdisulfide bonds between CD38 monomers [22]. In agreement with this hypothesis, studies carried out with porcine heart, rat lung and rat hepatocytes showed that under nonreducing conditions CD38 forms dimers, while under reducing conditions CD38 is present in a monomeric form [23][24][25]. On the other hand, Umar et al have shown that CD38 oligomers, expressed by retinoic acid stimulated HL60 cells, are covalently stabilized by transglutaminase, suggesting an alternate biochemical mechanism for the stabilization of covalent CD38 oligomers [26].…”

mentioning

confidence: 83%

CD38 is expressed as noncovalently associated homodimers on the surface of murine B lymphocytes

Moreno‐García

Partida-Sánchez

Primack

et al. 2004

European Journal of Biochemistry

View full text Add to dashboard Cite

CD38 is a transmembrane glycoprotein that functions as an ectoenzyme and as a receptor. Based on the structural similarity between CD38 and ADP-ribosyl cyclase from Aplysia californica, it was hypothesized that CD38 is expressed as a homodimer on the surface of cells. Indeed, CD38 dimers have been reported, however, the structural requirements for their stabilization on the plasma membrane are unknown. We demonstrate that the majority of CD38 is assembled as noncovalently associated homodimers on the surface of B cells. Analysis of CD38 mutants, expressed in Ba/F3 cells, revealed that truncation of the cytoplasmic region or mutation of a single amino acid within the a1-helix of CD38 decreased the stability of the CD38 homodimers when solubilized in detergent. Cells expressing the unstable CD38 homodimers had diminished expression of CD38 on the plasma membrane and the half-lives of these CD38 mutant proteins on the plasma membrane were significantly reduced. Together, these results show that CD38 is expressed as noncovalently associated homodimers on the surface of murine B cells and suggest that appropriate assembly of CD38 homodimers may play an important role in stabilizing CD38 on the plasma membrane of B cells.Keywords: B lymphocytes; CD38; homodimer stability; NAD + glycohydrolase; protein structure.CD38 is a type II transmembrane ectoenzyme expressed by many cell types [1][2][3]. CD38 plays an important role in calcium signaling as it catalyzes the production of several calcium mobilizing metabolites including adenosine(5¢)- [4,5]. In addition to its role as an enzyme, CD38 can also serve as a receptor on the plasma membrane of leukocytes and lymphocytes. For example, incubation of B lymphocytes with agonistic antibodies to CD38 induces calcium mobilization, protein phosphorylation, proliferation, class switching, rescue from cell death and induction of apoptosis [1,[6][7][8][9][10]. In order to understand the dual receptor and enzyme properties of CD38, a number of structure/function studies have been performed. These studies have been guided by analyses of two CD38 homologues, the cytosolic Aplysia californica ADP-ribosyl cyclase [11,12] and the mammalian GPI-anchored NAD + glycohydrolase, CD157 [13,14].Crystallographic and X-ray diffraction analyses of these two proteins indicated that both proteins form noncovalently associated homodimers [15,16]. Thus, it has been proposed that CD38 is also likely to be expressed as a homodimer on the plasma membrane and, in agreement with this hypothesis, initial reports showed that high molecular mass aggregates of CD38 are formed after incubation of human erythrocytes with NAD + or 2-mercaptoethanol [17]. In addition, it was reported that CD38 formed dimers and oligomers on the membrane of CD38 transfected HeLa cells [18]. It is not clear, however, whether CD38 is always present in a dimeric form on the surface of cells as many groups have reported finding only the monomeric form of CD38 [19][20][21]. Furthermore, it remains to be determined whether CD38 dimers ar...

show abstract

“…Indeed, we have found that the plasma membrane fraction isolated from hepatocytes contained abundant GDP-ribosyl cyclase activity (63). Upon using a different polyclonal antibody against CD38, we observed high immunoreactivity on the sinusoidal domain of rat hepatocytes but, surprisingly, the same antibody did not cross-react with the nuclear CD38 (63). It is possible that a different isoform or post-translationally modified form of CD38 is present on the nuclear envelope of the rat hepatocyte as compared with the plasma membrane CD38.…”

Section: Cadpr-dependent Ca 2ϩ -Signaling Pathway In the Nucleusmentioning

confidence: 99%

Localization of the Cyclic ADP-ribose-dependent Calcium Signaling Pathway in Hepatocyte Nucleus

Khoo¹,

Han²,

Park³

et al. 2000

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

CD38 is a type II transmembrane glycoprotein found on both hematopoietic and non-hematopoietic cells. It is known for its involvement in the metabolism of cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate, two nucleotides with calcium mobilizing activity independent of inositol trisphosphate. It is generally believed that CD38 is an integral protein with ectoenzymatic activities found mainly on the plasma membrane. Here we show that enzymatically active CD38 is present intracellularly on the nuclear envelope of rat hepatocytes. CD38 isolated from rat liver nuclei possessed both ADP-ribosyl cyclase and NADase activity. Immunofluorescence studies on rat liver cryosections and isolated nuclei localized CD38 to the nuclear envelope of hepatocytes. Subcellular localization via immunoelectron microscopy showed that CD38 is located on the inner nuclear envelope. The isolated nuclei sequestered calcium in an ATP-dependent manner. cADPR elicited a rapid calcium release from the loaded nuclei, which was independent of inositol trisphosphate and was inhibited by 8-amino-cADPR, a specific antagonist of cADPR, and ryanodine. However, nicotinic acid adenine dinucleotide phosphate failed to elicit any calcium release from the nuclear calcium stores. The nuclear localization of CD38 shown in this study suggests a novel role of CD38 in intracellular calcium signaling for non-hematopoietic cells.CD38 is a 42-45-kDa type II transmembrane glycoprotein (1) found in various mammalian tissues and cell types and is capable of converting NAD ϩ into cyclic ADP-ribose (cADPR) 1 (2). This ability is due to the ADP-ribosyl cyclase activity found on the extracellular carboxyl domain of the enzyme. The product, cADPR, possesses calcium mobilizing activity independent of inositol 1,4,5-trisphosphate (IP 3 ) (3). Instead, cADPR seems to regulate calcium mobilization through the calcium-inducedcalcium release mechanism (4, 5). In addition to cyclizing NAD ϩ to cADPR, CD38 is also able to use NADP ϩ as a substrate and catalyze the exchange of its nicotinamide group with nicotinic acid to produce NAADP (5), another potent calciummobilizing metabolite.CD38 is generally believed to be an important surface immunoregulatory molecule; its myriad of possible functions include the induction of B and T cell proliferation (6), regulation of the humoral immune response (7), apoptosis (8), tyrosine phosphorylation of various proteins (9), activation of certain kinases (10), and cytokine release (11). CD38 also displays adhesion properties and might possibly mediate a selectin-type adhesion between different blood populations and human vascular endothelial cells via its putative ligand, CD31 (12). In addition to its immuno-functions, CD38 has been shown to play an important role in insulin secretion via the cADPR-dependent calcium signaling pathway (13). Indeed, results suggest the appearance of autoantibodies to CD38 in patients may contribute to the development of noninsulin-dependent diabetes (14).The calcium stores mobilized by c...

show abstract

Localization of Plasma Membrane CD38 Is Domain Specific in Rat Hepatocyte

Cited by 18 publications

References 39 publications

Transformation and action of extracellular NAD+ in perfused rat and mouse livers

Transformation and action of extracellular NAD+ in perfused rat and mouse livers

CD38 is expressed as noncovalently associated homodimers on the surface of murine B lymphocytes

Localization of the Cyclic ADP-ribose-dependent Calcium Signaling Pathway in Hepatocyte Nucleus

Contact Info

Product

Resources

About