Cyclic ADP-ribose links metabolism to multiple fission in the dinoflagellate Crypthecodinium cohnii.
Cellular metabolism is required for cell proliferation. However, the way in which metabolic signals are conveyed to cell cycle decisions is unclear. Cyclic ADP-ribose (cADPR), the NAD(+) metabolite, mobilizes calcium from calcium stores in many cells. We found that dinoflagellate cells with higher metabolic rate underwent multiple fission (MF), a division mode in which cells can exceed twice their sizes at G1. A temperature shift-down experiment suggested that MF involves a commitment point at late G1. In fast-growing cells, cADPR level peaked in G(1) and increased with increasing concentrations of glucose in the medium. Addition of glycolytic poison iodoacetate inhibited cell growth, reduced cADPR levels as well as the commitment of cell cycles in fast-growing cells. Commitment of MF cell cycles was induced by a cell permeant cADPR agonist, but blocked by a specific antagonist of cADPR-induced Ca(2+) release. Our results establish cADPR as a link between cellular metabolism and cell cycle control.
Lam
Connie M C
CM
Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Yeung
Patrick K K
PK
Lee
Hon Cheung
HC
Wong
Joseph T Y
JT
D036541:ADP-ribosyl Cyclase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D004141:Dinoflagellida / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D005947:Glucose / Q000494:pharmacology; D007292:Inosine Nucleotides / Q000494:pharmacology; D007461:Iodoacetates / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D013696:Temperature
C493642:8-bromo-cyclic-ADP-ribose; D002614:Chelating Agents; D007292:Inosine Nucleotides; D007461:Iodoacetates; D007476:Ionophores; C107267:cyclic IDP-ribose; D009243:NAD; D036563:Cyclic ADP-Ribose; D036541:ADP-ribosyl Cyclase; D005947:Glucose; D002118:Calcium