Naslov
The effect of gangliosides on membrane ion transport in mouse brain

Autori
Mlinac Jerković, Kristina ; Puljko, Borna ; Stojanović, Mario ; Ilić, Katarina ; Maček Hrvat, Nikolina ; Damjanović, Vladimir ; Heffer, Marija ; Kalanj Bognar, Svjetlana

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

Izvornik
HDBMB22 From Science to Knowledge : book of abstracts / Dulić, Morana ; Sinčić, Nino ; Vrhovac Madunić, Ivana - Zagreb, 2022, 56-56

Skup
Congress of the Croatian Society of Biochemistry and Molecular Biology: From Science to Knowledge (HDBMB22)

Mjesto i datum
Brela, Hrvatska, 28.09.2022. - 01.10.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
glycosphingolipids ; gangliosides ; membrane ion transporters

Sažetak
Gangliosides, the most complex of all glycosphingolipids, carry approximately 75% of the brain's sialic acid. They are prominent constituents of neuronal membranes that serve not only as glycolipid scaffold of the membrane, but ligand-recognition partners as well. Gangliosides recognize and modulate the function of a multitude of specific proteins, including myelin-associated glycoprotein, TrkA receptor for the nerve growth factor and insulin receptor. In the last decade, several human diseases caused by the impaired biosynthesis of gangliosides have been reported. These congenital disorders of ganglioside biosynthesis include one form of hereditary spastic paraplegia and infantile-onset symptomatic epilepsy syndrome with symptoms ranging from motor deficits to cognitive deficits, epileptic seizures, hearing loss and intellectual disability. The molecular chain of events starting from aberrant ganglioside synthesis and leading towards this phenotype has not yet been explained. The long-standing goal of our research group is to clarify specific roles of gangliosides by studying their interactions with specific proteins. By using in vitro model systems, cell culture models as well as mouse models with deficient ganglioside synthesis, we identified several membrane ion transporters and their protein partners as being heavily influenced by ganglioside microenvironment of the membrane. Those include Na⁺/K⁺-ATPase (NKA), plasma membrane Ca2+-ATPase (PMCA), and the PMCA partner neuroplastin. We used gene expression analysis, protein expression analysis by Western blotting and immunohistochemistry, enzyme activity determination, submembrane localization analysis in mouse models with deficient ganglioside biosynthesis, in addition to analysis of the effects of exogenously added gangliosides and anti-ganglioside antibodies in cell culture and tissue homogenates. By using this comprehensive approach which encompasses all the crucial stages in the regulation and function of a protein - gene expression level, protein expression level, correct positioning of the protein and the ultimate enzyme activity - we unequivocally show that specific gangliosides contribute to brain ion homeostasis by regulating the expression and micro-positioning of specific ion transporters.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA