Naslov
Gangliosides framework for optimal function of plasma membrane ion transporters

Autori
Mlinac Jerković, Kristina

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

Izvornik
8th Croatian neuroscience congress : book of abstracts / - Zagreb, 2021, 38-38

Skup
8th Croatian neuroscience congress

Mjesto i datum
Online, 24.09.2021. - 25.09.2021

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
lipid rafts ; glycosphingolipids ; PMCA ; sodium potassium ATPase

Sažetak
Lipid-protein interactions determine the proper positioning and function of plasma membrane proteins. Plasma membrane is not a simple homogeneous cellular envelope, but a highly dynamic structure resembling a patchwork of lipid raft microdomains with distinct composition and physicochemical properties. These nanometer-scale submembrane compartments are enriched with (glyco)sphingolipids, cholesterol, and a select subset of transmembrane proteins. Hence, lipid- protein interdependence and functional interplay is markedly highlighted in these domains. Gangliosides, the most complex glycosphingolipids, have many documented effects including modulation of ion homeostasis. Since the neuronal membrane shows the highest concentration and compositional diversity of gangliosides, their effect on plasma membrane ion transporters involved in membrane potential generation and maintenance is of special interest. Gangliosides are shown to have effects on Na+, K+- ATPase (NKA), as well as plasma membrane calcium- ATPase (PMCA). Depending on the number of sialic acids present in the ganglioside structure, they can have stimulatory or inhibitory effect on PMCA. Therefore, the complexity of ganglioside structures can fine-tune PMCA activity and affect the Ca2+ ions extrusion from the cell. Our group has shown that specific gangliosides are necessary for providing the appropriate structural framework for the positioning and consequently normal function of PMCA, complexed with its essential auxiliary subunit, glycoprotein neuroplastin. In addition, the dual role of gangliosides in the supramolecular architecture of submembrane domains is documented for NKA as well. As we have shown, gangliosides GD1a, GD1b and GT1b having notably richer topology may serve as modulators of NKA activity, while GM1 may have a structurally supporting role for NKA positioning and assembling within the lipid rafts or bulk membrane microdomain. Disturbances in the lipid environment of the membrane are well recognized as potential driving factors in the pathogenesis of several human disorders. However, the mechanism leading from changed ganglioside composition of the membrane to the clinical presentation of these diseases remains an enigma. Hopefully, the work elucidating the exact effect of gangliosides on plasma membrane ion transporters in the brain will facilitate understading of ethiopathology of these complex disorders, as well as contribute to fundamental knowledge of ion homeostasis regulation in the brain.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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