title: CD38/CD19: a lipid raft-dependent signaling complex in human B cells.
abstract: The present work deals with the mechanisms of signal transduction mediated via CD38 in normal and neoplastic human B lymphocytes. The results indicate that CD38 is a receptor and that CD38-mediated signals are tightly regulated at 3 distinct levels. The first concerns the structural organization of CD38, which is clearly divided into monomeric and dimeric forms. The second level of regulation is based on the dynamic localization of CD38 molecules in lipid microdomains within the plasma membrane. Lateral associations with other proteins, namely with the CD19/CD81 complex, determine the third level of control. Raft localization and association with the CD19 complex are prerequisites for CD38-mediated signals in tonsillar B cells and in continuous lines. Lastly, the results indicate that lipid microdomain disruption and silencing of CD19 directly impacts on CD38's ability to mediate Ca(2+) fluxes, while leaving its surface expression unchanged. CD38 is also an enzyme capable of producing several calcium-mobilizing metabolites including cyclic adenosine diphosphate ribose (cADPR). Our inability to identify a correlation between the production of cADPR and the receptorial functions support the hypothesis that CD38 is a pleiotropic molecule whose behavior as a receptor is independent from its enzymatic activity.
authors.affiliation: Department of Genetics, Biology and Biochemistry, University of Torino Medical School, Torino, Italy. silvia.deglio@unito.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Deaglio
authors.forename: Tiziana
authors.initials: T
authors.lastname: Vaisitti
authors.forename: Richard
authors.initials: R
authors.lastname: Billington
authors.forename: Luciana
authors.initials: L
authors.lastname: Bergui
authors.forename: Paola
authors.initials: P
authors.lastname: Omede'
authors.forename: Armando A
authors.initials: AA
authors.lastname: Genazzani
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000502:physiology*; D018941:Antigens, CD19 / Q000502:physiology*; D001402:B-Lymphocytes / Q000737:chemistry*; D020013:Calcium Signaling; D002460:Cell Line; D045744:Cell Line, Tumor; D019281:Dimerization; D006801:Humans; D021962:Membrane Microdomains / Q000502:physiology*; D011485:Protein Binding; D011956:Receptors, Cell Surface; D015398:Signal Transduction
chemical_list: D018941:Antigens, CD19; D011956:Receptors, Cell Surface; D051997:ADP-ribosyl Cyclase 1