Role of Huntingtin-associated protein 1 in the regulation of SOCE in medium spiny neurons from transgenic YAC128 mice, a model of Huntington's disease

• Autorzy: Czeredys M. , Maciag F. , Vigont V. , Kaznacheyeva E. , Methner A. , Kuznicki J.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Huntington’s disease (HD) is a hereditary neurodegenerative disease caused by the expansion of a polyglutamine stretch in the huntingtin (HTT) protein and characterized by deregulated Ca2+ homeostasis (Giacomello et al. 2013). One of the mechanisms that regulate Ca2+ homeostasis is store-operated Ca2+ entry (SOCE) (Majewski and Kuźnicki 2015), which is enhanced in HD (Wu et al. 2011). The mechanism by which mutated HTT affects SOCE is unknown. The changes in Ca2+ homeostasis could be explained by increased expression of huntingtin-associated protein 1 (Hap1) mRNA (3-fold) and HAP1 protein (about 2-fold) in the striatum of YAC128 mice, which we detected (Czeredys et al. 2013). If HAP1 influences ER Ca2+ release mediated by IP3R in MSN from YAC128 mice, which was shown in other HD models by Tang et al. (2003, 2004), its increased level may explain changes in SOCE described by Wu et al. (2011). The aim of this study is to determine the role of HAP1 protein in the regulation of SOCE in MSN from transgenic mice YAC128, an HD model. METHODS: Using prepared lentiviral constructs we overexpressed HAP1a or HAP1b in YAC128 neurons, and in HEK293 cells overexpressing mutant HTT. We imaged cells with Fura-2AM, a selective fluorescent Ca2+ probe. SOCE was measured after depletion of intracellular Ca2+ by mGluR1/5 receptor agonist, DHPG (3,5- dihydroxyglycine) and subsequent incubation of cells in 2 mM Ca2+ media. RESULTS: In HD MSN we detected about 10% increase in basal Ca2+ level and found that the activity of SOCE was enhanced about 30%, thereby confirming results of Wu et al. (2011). The preliminary results showed that overexpressed Hap1 protein is involved in SOCE pathway in studied cells. Using electrophysiology we will also determine changes in the SOC currents in MSN and SK-N-SH cells, both transduced with HAP1 and mutant HTT. CONCLUSION: The investigation of the role of HAP1 protein in deregulated.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S41

Twórcy

autor

Czeredys M.

• International Institute of Molecular and Cell Biology, Warsaw, Poland

autor

Maciag F.

• International Institute of Molecular and Cell Biology, Warsaw, Poland
• Warsaw University of Technology, Warsaw, Poland

autor

Vigont V.

• Warsaw University of Technology, Warsaw, Poland

autor

Kaznacheyeva E.

• Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia

autor

Methner A.

• Johannes Gutenberg University Medical Center Mainz, Mainz, Germany

autor

Kuznicki J.

• International Institute of Molecular and Cell Biology, Warsaw, Poland