Huntingtin-Associated Protein 1A Regulates Store-Operated Calcium Entry in Medium Spiny Neurons From Transgenic YAC128 Mice, a Model of Huntington’s Disease
Huntington’s disease (HD) is a hereditary neurodegenerative disease that is caused by polyglutamine expansion within the huntingtin (HTT) gene. One of the cellular activities that is dysregulated in HD is store-operated calcium entry (SOCE), a process by which Ca2+ release from the endoplasmic retic...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-10-01
|
| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2018.00381/full |
| _version_ | 1811278201590120448 |
|---|---|
| author | Magdalena Czeredys Vladimir A. Vigont Vasilisa A. Boeva Katsuhiko Mikoshiba Elena V. Kaznacheyeva Jacek Kuznicki |
| author_facet | Magdalena Czeredys Vladimir A. Vigont Vasilisa A. Boeva Katsuhiko Mikoshiba Elena V. Kaznacheyeva Jacek Kuznicki |
| author_sort | Magdalena Czeredys |
| collection | DOAJ |
| description | Huntington’s disease (HD) is a hereditary neurodegenerative disease that is caused by polyglutamine expansion within the huntingtin (HTT) gene. One of the cellular activities that is dysregulated in HD is store-operated calcium entry (SOCE), a process by which Ca2+ release from the endoplasmic reticulum (ER) induces Ca2+ influx from the extracellular space. HTT-associated protein-1 (HAP1) is a binding partner of HTT. The aim of the present study was to examine the role of HAP1A protein in regulating SOCE in YAC128 mice, a transgenic model of HD. After Ca2+ depletion from the ER by the activation of inositol-(1,4,5)triphosphate receptor type 1 (IP3R1), we detected an increase in the activity of SOC channels when HAP1 protein isoform HAP1A was overexpressed in medium spiny neurons (MSNs) from YAC128 mice. A decrease in the activity of SOC channels in YAC128 MSNs was observed when HAP1 protein was silenced. In YAC128 MSNs that overexpressed HAP1A, an increase in activity of IP3R1 was detected while the ionomycin-sensitive ER Ca2+ pool decreased. 6-Bromo-N-(2-phenylethyl)-2,3,4,9-tetrahydro-1H-carbazol-1-amine hydrochloride (C20H22BrClN2), identified in our previous studies as a SOCE inhibitor, restored the elevation of SOCE in YAC128 MSN cultures that overexpressed HAP1A. The IP3 sponge also restored the elevation of SOCE and increased the release of Ca2+ from the ER in YAC128 MSN cultures that overexpressed HAP1A. The overexpression of HAP1A in the human neuroblastoma cell line SK-N-SH (i.e., a cellular model of HD (SK-N-SH HTT138Q)) led to the appearance of a pool of constitutively active SOC channels and an increase in the expression of STIM2 protein. Our results showed that HAP1A causes the activation of SOC channels in HD models by affecting IP3R1 activity. |
| first_indexed | 2024-04-13T00:30:25Z |
| format | Article |
| id | doaj.art-c7e5689de540475f80284f94549c32ff |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-13T00:30:25Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-c7e5689de540475f80284f94549c32ff2022-12-22T03:10:29ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022018-10-011210.3389/fncel.2018.00381417838Huntingtin-Associated Protein 1A Regulates Store-Operated Calcium Entry in Medium Spiny Neurons From Transgenic YAC128 Mice, a Model of Huntington’s DiseaseMagdalena Czeredys0Vladimir A. Vigont1Vasilisa A. Boeva2Katsuhiko Mikoshiba3Elena V. Kaznacheyeva4Jacek Kuznicki5Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology in Warsaw (IIMCB), Warsaw, PolandInstitute of Cytology, Russian Academy of Sciences (RAS), St. Petersburg, RussiaInstitute of Cytology, Russian Academy of Sciences (RAS), St. Petersburg, RussiaLaboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), Saitama, JapanInstitute of Cytology, Russian Academy of Sciences (RAS), St. Petersburg, RussiaLaboratory of Neurodegeneration, International Institute of Molecular and Cell Biology in Warsaw (IIMCB), Warsaw, PolandHuntington’s disease (HD) is a hereditary neurodegenerative disease that is caused by polyglutamine expansion within the huntingtin (HTT) gene. One of the cellular activities that is dysregulated in HD is store-operated calcium entry (SOCE), a process by which Ca2+ release from the endoplasmic reticulum (ER) induces Ca2+ influx from the extracellular space. HTT-associated protein-1 (HAP1) is a binding partner of HTT. The aim of the present study was to examine the role of HAP1A protein in regulating SOCE in YAC128 mice, a transgenic model of HD. After Ca2+ depletion from the ER by the activation of inositol-(1,4,5)triphosphate receptor type 1 (IP3R1), we detected an increase in the activity of SOC channels when HAP1 protein isoform HAP1A was overexpressed in medium spiny neurons (MSNs) from YAC128 mice. A decrease in the activity of SOC channels in YAC128 MSNs was observed when HAP1 protein was silenced. In YAC128 MSNs that overexpressed HAP1A, an increase in activity of IP3R1 was detected while the ionomycin-sensitive ER Ca2+ pool decreased. 6-Bromo-N-(2-phenylethyl)-2,3,4,9-tetrahydro-1H-carbazol-1-amine hydrochloride (C20H22BrClN2), identified in our previous studies as a SOCE inhibitor, restored the elevation of SOCE in YAC128 MSN cultures that overexpressed HAP1A. The IP3 sponge also restored the elevation of SOCE and increased the release of Ca2+ from the ER in YAC128 MSN cultures that overexpressed HAP1A. The overexpression of HAP1A in the human neuroblastoma cell line SK-N-SH (i.e., a cellular model of HD (SK-N-SH HTT138Q)) led to the appearance of a pool of constitutively active SOC channels and an increase in the expression of STIM2 protein. Our results showed that HAP1A causes the activation of SOC channels in HD models by affecting IP3R1 activity.https://www.frontiersin.org/article/10.3389/fncel.2018.00381/fullHuntington’s diseasehuntingtinhuntingtin-associated protein 1 isoform AYAC128medium spiny neuronsstore-operated calcium entry |
| spellingShingle | Magdalena Czeredys Vladimir A. Vigont Vasilisa A. Boeva Katsuhiko Mikoshiba Elena V. Kaznacheyeva Jacek Kuznicki Huntingtin-Associated Protein 1A Regulates Store-Operated Calcium Entry in Medium Spiny Neurons From Transgenic YAC128 Mice, a Model of Huntington’s Disease Frontiers in Cellular Neuroscience Huntington’s disease huntingtin huntingtin-associated protein 1 isoform A YAC128 medium spiny neurons store-operated calcium entry |
| title | Huntingtin-Associated Protein 1A Regulates Store-Operated Calcium Entry in Medium Spiny Neurons From Transgenic YAC128 Mice, a Model of Huntington’s Disease |
| title_full | Huntingtin-Associated Protein 1A Regulates Store-Operated Calcium Entry in Medium Spiny Neurons From Transgenic YAC128 Mice, a Model of Huntington’s Disease |
| title_fullStr | Huntingtin-Associated Protein 1A Regulates Store-Operated Calcium Entry in Medium Spiny Neurons From Transgenic YAC128 Mice, a Model of Huntington’s Disease |
| title_full_unstemmed | Huntingtin-Associated Protein 1A Regulates Store-Operated Calcium Entry in Medium Spiny Neurons From Transgenic YAC128 Mice, a Model of Huntington’s Disease |
| title_short | Huntingtin-Associated Protein 1A Regulates Store-Operated Calcium Entry in Medium Spiny Neurons From Transgenic YAC128 Mice, a Model of Huntington’s Disease |
| title_sort | huntingtin associated protein 1a regulates store operated calcium entry in medium spiny neurons from transgenic yac128 mice a model of huntington s disease |
| topic | Huntington’s disease huntingtin huntingtin-associated protein 1 isoform A YAC128 medium spiny neurons store-operated calcium entry |
| url | https://www.frontiersin.org/article/10.3389/fncel.2018.00381/full |
| work_keys_str_mv | AT magdalenaczeredys huntingtinassociatedprotein1aregulatesstoreoperatedcalciumentryinmediumspinyneuronsfromtransgenicyac128miceamodelofhuntingtonsdisease AT vladimiravigont huntingtinassociatedprotein1aregulatesstoreoperatedcalciumentryinmediumspinyneuronsfromtransgenicyac128miceamodelofhuntingtonsdisease AT vasilisaaboeva huntingtinassociatedprotein1aregulatesstoreoperatedcalciumentryinmediumspinyneuronsfromtransgenicyac128miceamodelofhuntingtonsdisease AT katsuhikomikoshiba huntingtinassociatedprotein1aregulatesstoreoperatedcalciumentryinmediumspinyneuronsfromtransgenicyac128miceamodelofhuntingtonsdisease AT elenavkaznacheyeva huntingtinassociatedprotein1aregulatesstoreoperatedcalciumentryinmediumspinyneuronsfromtransgenicyac128miceamodelofhuntingtonsdisease AT jacekkuznicki huntingtinassociatedprotein1aregulatesstoreoperatedcalciumentryinmediumspinyneuronsfromtransgenicyac128miceamodelofhuntingtonsdisease |