Ruling out pyridine dinucleotides as true TRPM2 channel activators reveals novel direct agonist ADP-ribose-2'-phosphate

Toth, B [Tóth, Balázs (elektrofiziológia), szerző] Orvosi Biokémiai Intézet (SE / AOK / I); Iordanov, I [Iordanov, Iordan (biokémia), szerző] Orvosi Biokémiai Intézet (SE / AOK / I); Csanady, L ✉ [Csanády, László (Biokémia), szerző] MTA-SE Lendület Ioncsatorna Kutatócsoport (SE / AOK / I / BMBI / BT)

Angol nyelvű Tudományos Szakcikk (Folyóiratcikk)
Megjelent: JOURNAL OF GENERAL PHYSIOLOGY 0022-1295 1540-7748 145 (5) pp. 419-430 2015
  • SJR Scopus - Physiology: D1
Azonosítók
Szakterületek:
    Transient receptor potential melastatin 2 (TRPM2), a Ca(2+)-permeable cation channel implicated in postischemic neuronal cell death, leukocyte activation, and insulin secretion, is activated by intracellular ADP ribose (ADPR). In addition, the pyridine dinucleotides nicotinamide-adenine-dinucleotide (NAD), nicotinic acid-adenine-dinucleotide (NAAD), and NAAD-2'-phosphate (NAADP) have been shown to activate TRPM2, or to enhance its activation by ADPR, when dialyzed into cells. The precise subset of nucleotides that act directly on the TRPM2 protein, however, is unknown. Here, we use a heterologously expressed, affinity-purified-specific ADPR hydrolase to purify commercial preparations of pyridine dinucleotides from substantial contaminations by ADPR or ADPR-2'-phosphate (ADPRP). Direct application of purified NAD, NAAD, or NAADP to the cytosolic face of TRPM2 channels in inside-out patches demonstrated that none of them stimulates gating, or affects channel activation by ADPR, indicating that none of these dinucleotides directly binds to TRPM2. Instead, our experiments identify for the first time ADPRP as a true direct TRPM2 agonist of potential biological interest.
    Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSLMásolásNyomtatás
    2021-11-30 06:28