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- W48871004 abstract "Az ABC transzporterek egy ősi feherjecsalad tagjai, melyek az emlős sejtekben is szerteagazo funkciokkal birnak. Altalunk vizsgalt tagjuk a human P-glikoprotein (Pgp), melyet a tumorok kemoterapiajanak meghiusitasa alapjan azonositottak. Kiderult, hogy lenyeges a fiziologias es a karos lipofil anyagoknak a normal sejtekből valo eltavolitasaban is. Munkankban kimutattuk, hogy a Pgp transzport koleszterinfuggő. A koleszterin az emlős sejtek membranjanak egyik komponense, mely a szfingolipidekkel es feherjekkel egyutt egy funkcionalis egyseget, un. raftokat hoz letre a membranon belul. Munkankbol kiderult, hogy a Pgp a raftok egyik komponense, es a Pgpnek a citoszkeletonhoz es a raftokhoz valo kapcsoltsaga is koleszterinfuggő. Projektunkben e jelensegkor altalanos vizsgalatara alkalmas citometrias modszert fejlesztettunk ki. Felismertuk, hogy a Pgpnek a raftokhoz es a citoszkeletonhoz valo szerkezeti kapcsoltsaga a Pgp traffickingjevel magyarazhato. Ket fajta Pgp molekulat sikerult ugyanis azonositanunk, melyek endocitozisa kulonboző sebessegű. A koleszterin kapcsolt endocitozis sokkal gyorsabb, mint a koleszterin fuggetlen. A Pgpnek e ket fajtaja mas-mas konformacioju es mas-mas citoszkeletalis feherjekkel alakit ki kapcsolatokat a sejtben. Munkank azon globalis kephez visz kozelebb bennunket, hogy miert lehet fontos az emlős sejtek evoluciojaban a koleszterin. Segitsegevel ugyanis egy olyan autoregulacio johet letre, mely kepes a membran feherjeket sejtmembranban tartani. | ABC-transporters, members of an ancient protein family, evolved complex functions in mammalian cells. One of their members examined by us is the human P-glycoprotein (Pgp) was discovered based on its role played in thwarting tumor chemotherapy. Pgp eliminates harmful and physiologic lipophilic substances from normal cells, as well. We have showed that transport function of the Pgp is cholesterol dependent. The cholesterol and sphingolipids, together with different proteins may form so-called membrane rafts, considered as important functional units of mammalian cell membranes. We observed that Pgp is a raft constituent. Structural association of the Pgp to rafts and to the cytoskeleton shows cholesterol dependence similar to its cholesterol dependent transporter function. We have developed a screening method for evaluating the raft association of proteins in single cells. We realized that raft and cytoskeleton association of the Pgp comprehended with their trafficking. We have identified two kinds of Pgp molecules with two different endocytotic velocities. The cholesterol connected endocytosis was much faster, than the cholesterol independent. Furthermore, the two Pgp molecules have different actin binding protein partners. Our work takes us to the global picture why cholesterol is important in the evolution of the mammalian cells. Cholesterol probably generates an auto regulatory circle in the membrane, which insures keeping functional proteins in the cell membrane." @default.
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- W48871004 date "2008-01-01" @default.
- W48871004 modified "2023-09-23" @default.
- W48871004 title "ABC transzporterek fiziológiás szerepkörökben = ABC transporters in physiological contexts" @default.
- W48871004 hasPublicationYear "2008" @default.
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