A new function for CD38/ADP-ribosyl cyclase in nuclear Ca2+ homeostasis.
Nucleoplasmic calcium ions (Ca2+) influence nuclear functions as critical as gene transcription, apoptosis, DNA repair, topoisomerase activation and polymerase unfolding. Although both inositol trisphosphate receptors and ryanodine receptors, types of Ca2+ channel, are present in the nuclear membrane, their role in the homeostasis of nuclear Ca2+ remains unclear. Here we report the existence in the inner nuclear membrane of a functionally active CD38/ADP-ribosyl cyclase that has its catalytic site within the nucleoplasm. We propose that the enzyme catalyses the intranuclear cyclization of nicotinamide adenine dinucleotide to cyclic adenosine diphosphate ribose. The latter activates ryanodine receptors of the inner nuclear membrane to trigger nucleoplasmic Ca2+ release.
Adebanjo
O A
OA
Department of Medicine, Medical College of Pennsylvania School of Medicine and Veterans Affairs Medical Center, Philadelphia, Pennsylvania 19104, USA.
Anandatheerthavarada
H K
HK
Koval
A P
AP
Moonga
B S
BS
Biswas
G
G
Sun
L
L
Sodam
B R
BR
Bevis
P J
PJ
Huang
C L
CL
Epstein
S
S
Lai
F A
FA
Avadhani
N G
NG
Zaidi
M
M
D016475:3T3 Cells; D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002458:Cell Fractionation / Q000379:methods; D002467:Cell Nucleus / Q000378:metabolism*; D036563:Cyclic ADP-Ribose; D017930:Genes, Reporter / Q000235:genetics; D015151:Immunoblotting; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008562:Membrane Glycoproteins; D051379:Mice; D018613:Microscopy, Confocal; D009097:Multienzyme Complexes; D009243:NAD / Q000494:pharmacology; D009244:NAD+ Nucleosidase / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D009097:Multienzyme Complexes; D011993:Recombinant Fusion Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D009243:NAD; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D015544:Inositol 1,4,5-Trisphosphate; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium