CD38 controls ADP-ribosyltransferase-2-catalyzed ADP-ribosylation of T cell surface proteins
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CD38 controls ADP-ribosyltransferase-2-catalyzed ADP-ribosylation of T cell surface proteins. / Krebs, Christian; Adriouch, Sahil; Braasch, Fenja; Koestner, Wolfgang; Leiter, Edward H; Seman, Michel; Lund, Frances E; Oppenheimer, Norman; Haag, Friedrich; Koch-Nolte, Friedrich.
In: J IMMUNOL, Vol. 174, No. 6, 15.03.2005, p. 3298-305.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - CD38 controls ADP-ribosyltransferase-2-catalyzed ADP-ribosylation of T cell surface proteins
AU - Krebs, Christian
AU - Adriouch, Sahil
AU - Braasch, Fenja
AU - Koestner, Wolfgang
AU - Leiter, Edward H
AU - Seman, Michel
AU - Lund, Frances E
AU - Oppenheimer, Norman
AU - Haag, Friedrich
AU - Koch-Nolte, Friedrich
PY - 2005/3/15
Y1 - 2005/3/15
N2 - ADP-ribosyltransferase-2 (ART2), a GPI-anchored, toxin-related ADP-ribosylating ectoenzyme, is prominently expressed by murine T cells but not by B cells. Upon exposure of T cells to NAD, the substrate for ADP-ribosylation, ART2 catalyzes ADP-ribosylation of the P2X7 purinoceptor and other functionally important cell surface proteins. This in turn activates P2X7 and induces exposure of phosphatidylserine and shedding of CD62L. CD38, a potent ecto-NAD-glycohydrolase, is strongly expressed by most B cells but only weakly by T cells. Following incubation with NAD, CD38-deficient splenocytes exhibited lower NAD-glycohydrolase activity and stronger ADP-ribosylation of cell surface proteins than their wild-type counterparts. Depletion of CD38(high) cells from wild-type splenocytes resulted in stronger ADP-ribosylation on the remaining cells. Similarly, treatment of total splenocytes with the CD38 inhibitor nicotinamide 2'-deoxy-2'-fluoroarabinoside adenine dinucleotide increased the level of cell surface ADP-ribosylation. Furthermore, the majority of T cells isolated from CD38-deficient mice "spontaneously" exposed phosphatidylserine and lacked CD62L, most likely reflecting previous encounter with ecto-NAD. Our findings support the notion that ecto-NAD functions as a signaling molecule following its release from cells by lytic or nonlytic mechanisms. ART2 can sense and translate the local concentration of ecto-NAD into corresponding levels of ADP-ribosylated cell surface proteins, whereas CD38 controls the level of cell surface protein ADP-ribosylation by limiting the substrate availability for ART2.
AB - ADP-ribosyltransferase-2 (ART2), a GPI-anchored, toxin-related ADP-ribosylating ectoenzyme, is prominently expressed by murine T cells but not by B cells. Upon exposure of T cells to NAD, the substrate for ADP-ribosylation, ART2 catalyzes ADP-ribosylation of the P2X7 purinoceptor and other functionally important cell surface proteins. This in turn activates P2X7 and induces exposure of phosphatidylserine and shedding of CD62L. CD38, a potent ecto-NAD-glycohydrolase, is strongly expressed by most B cells but only weakly by T cells. Following incubation with NAD, CD38-deficient splenocytes exhibited lower NAD-glycohydrolase activity and stronger ADP-ribosylation of cell surface proteins than their wild-type counterparts. Depletion of CD38(high) cells from wild-type splenocytes resulted in stronger ADP-ribosylation on the remaining cells. Similarly, treatment of total splenocytes with the CD38 inhibitor nicotinamide 2'-deoxy-2'-fluoroarabinoside adenine dinucleotide increased the level of cell surface ADP-ribosylation. Furthermore, the majority of T cells isolated from CD38-deficient mice "spontaneously" exposed phosphatidylserine and lacked CD62L, most likely reflecting previous encounter with ecto-NAD. Our findings support the notion that ecto-NAD functions as a signaling molecule following its release from cells by lytic or nonlytic mechanisms. ART2 can sense and translate the local concentration of ecto-NAD into corresponding levels of ADP-ribosylated cell surface proteins, whereas CD38 controls the level of cell surface protein ADP-ribosylation by limiting the substrate availability for ART2.
KW - ADP Ribose Transferases
KW - ADP-ribosyl Cyclase
KW - Adenosine Diphosphate Ribose
KW - Animals
KW - Antigens, CD
KW - Antigens, CD38
KW - Immunomagnetic Separation
KW - In Vitro Techniques
KW - L-Selectin
KW - Membrane Glycoproteins
KW - Membrane Proteins
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - NAD
KW - Phosphatidylserines
KW - T-Lymphocytes
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
KW - Research Support, U.S. Gov't, P.H.S.
M3 - SCORING: Journal article
C2 - 15749861
VL - 174
SP - 3298
EP - 3305
JO - J IMMUNOL
JF - J IMMUNOL
SN - 0022-1767
IS - 6
ER -