Naslov
IRBIT, a Inositol 1, 4, 5-trisphosphate receptor (IP3R) binding protein specifically binds to and inactivates S-adenosyl-L-homocysteine hydrolase

Autori
Grbeša, Ivana ; Kovačević, Lucija ; Belužić, Robert ; Lepur, Adriana ; Knežević, Jelena ; Trmčić Cvitaš, Jelena ; Munoz Torres, Pau Marc ; Vugrek, Oliver

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
The FEBS Journal Special Issue: FEBS EMBO 2014 Conference, Paris, France, 30 August-4 September 2014 / - Pariz : John Wiley & Sons, 2014, 577-577

Skup
FEBS EMBO 2014 Conference

Mjesto i datum
Pariz, Francuska, 30.08.2014. - 04.09.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
AHCY, IRBIT, S-Adenosyl homocysteine

Sažetak
Predominantly, S-adenosylhomocysteine hydrolase (AHCY) is a cytoplasmic, homotetrameric enzyme, but some portion of the protein is located to the nucleus. Indeed, it is proposed that the efficiency of transmethylation might profit from a close proximity between methyltransferases and AHCY due to its particular function of rapid removal of S-adenosyl homocysteine (SAH), the byproduct of transmethylation reactions. Rapid removal of SAH is crucial to avoid product inhibition of methyltransferases as it is one of the most potent methyltransferase inhibitors. Very little is known in terms of regulation of enzymatic activity of AHCY, nor its intracellular dynamics. Devogelaere et al (2008) hypothesized that AHCY might interact with a homologous protein, namely S-adenosyl-L- homocystein hydrolase-like protein (AHCYL1, IRBIT). In an effort to evaluate putative interactions between AHCY and AHCYL1 we used molecular, biochemical and cell biological approaches. We performed functional studies of recombinant proteins, Co-IP experiments, FRET in combination with confocal microscopy and live cell imaging, and mass spectrometry. In view of our studies we have confirmed that AHCYL1 specifically binds to and inactivates S- adenosylhomocysteine hydrolase. Our results show that besides documented functions of AHCYL1 as inhibitor of inositol 1, 4, 5-trisphosphate receptor (IP3R), and activator of Na+/HCO3 co-transporters (NBC), AHCYL1 has an additional role thus interacting with AHCY and regulating its function. This indicates crosstalk between Ca2+ regulation, intracellular pH, methylation potential regulation, and signaling between cytoplasm and the nucleus shedding new light on the AHCY family of proteins.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA