title: Localization of CD38 in murine B lymphocytes to plasma but not intracellular membranes.
abstract: CD38 has been widely characterized both as an ecto-enzyme and as a receptor. As an enzyme, CD38 catalyzes the conversion of NAD(+) and NADP to several metabolites including cADPR and NAADP, which mediate Ca(2+) release from separate intracellular stores, and ADPR, which activates the TRPM2 plasma membrane Ca(2+) channel. Since the catalytic domain of CD38 is exposed to the extracellular milieu, several mechanistic and topological studies have been performed to explain how CD38 gains access to its substrates, which are found at highest concentration in the cytosol of cells, and how the non-permeant metabolites produced by ecto-CD38 arrive at their intracellular site(s) of action. Accordingly, several studies have reported that CD38 is not only expressed on the plasma membrane but is also found in various sub-cellular compartments, including the nucleus where it is localized to the inner nuclear membrane. In this work, we employed a protocol of mild membrane solubilization to cleanly separate plasma membranes from other intracellular membranes and then analyzed the sub-cellular expression of murine CD38 in purified primary B lymphocytes. After immunoprecipitation, CD38 was exclusively detected in the plasma membrane protein containing soluble fraction and not in the insoluble fraction which was highly enriched for nuclear, endoplasmic reticulum and mitochondrial proteins. Likewise, NAD(+) glycohydrolase measurements and confocal microscopy analysis corroborated that CD38 was not localized in nuclear membranes and indicated that CD38 is primarily, if not exclusively, localized to the plasma membrane of murine B lymphocytes.
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y Estudios Avanzados del I.P.N., Apartado Postal 14-740, CP 07360 México D.F., México.
authors.forename: Miguel E
authors.initials: ME
authors.lastname: Moreno-García
authors.forename: Adriana
authors.initials: A
authors.lastname: Sumoza-Toledo
authors.forename: Frances E
authors.initials: FE
authors.lastname: Lund
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Santos-Argumedo
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000276:immunology* / Q000378:metabolism; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism; D005260:Female; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal
chemical_list: D015703:Antigens, CD; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1