Huntingtin-Associated Protein 1A Regulates Store-Operated Calcium Entry in Medium Spiny Neurons From Transgenic YAC128 Mice, a Model of Huntington’s Disease

Czeredys, Magdalena; Vigont, Vladimir; Boeva, Vasilisa A.; Mikoshiba, Katsuhiko; Kaznacheyeva, Еlena; Kuźnicki, Jacek

doi:10.3389/fncel.2018.00381

Cited by 23 publications

(28 citation statements)

References 60 publications

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“…Recent studies showed that the expression of huntingtin-associated protein 1A (HAP1) was elevated in the striatum in a mouse model of HD [113]. HAP1, similar to mHTT, activated SOCE by influencing IP 3 R1 [113,114]. In human neuroblastoma cells, the HD pathological phenotype was mediated by expression of the N-terminal fragment of mHTT, which increased SOCE in a STIM1-dependent manner [115].…”

Section: Relationship Between Stim Proteins Glutamate and Glutammentioning

confidence: 99%

STIM Proteins and Glutamate Receptors in Neurons: Role in Neuronal Physiology and Neurodegenerative Diseases

Serwach

Gruszczynska-Biegala

2019

IJMS

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Neuronal calcium (Ca2+) influx has long been ascribed mainly to voltage-gated Ca2+ channels and glutamate receptor channels. Recent research has shown that it is also complemented by stromal interaction molecule (STIM) protein-mediated store-operated Ca2+ entry (SOCE). SOCE is described as Ca2+ flow into cells in response to the depletion of endoplasmic reticulum Ca2+ stores. The present review summarizes recent studies that indicate a relationship between neuronal SOCE that is mediated by STIM1 and STIM2 proteins and glutamate receptors under both physiological and pathological conditions, such as neurodegenerative disorders. We present evidence that the dysregulation of neuronal SOCE and glutamate receptor activity are hallmarks of acute neurodegenerative diseases (e.g., traumatic brain injury and cerebral ischemia) and chronic neurodegenerative diseases (e.g., Alzheimer’s disease and Huntington’s disease). Emerging evidence indicates a role for STIM proteins and glutamate receptors in neuronal physiology and pathology, making them potential therapeutic targets.

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Section: Relationship Between Stim Proteins Glutamate and Glutammentioning

confidence: 99%

STIM Proteins and Glutamate Receptors in Neurons: Role in Neuronal Physiology and Neurodegenerative Diseases

Serwach

Gruszczynska-Biegala

2019

IJMS

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“…SOCE has been implicated in various neuronal functions, such as neuronal plasticity [15,17], the expression and activity of PM receptors [18,19], neuronal excitability [6,20], and the regulation of gene expression [16]. Disruptions of SOCE have been implicated in several neurodegenerative diseases, including Alzheimer's disease [17,21], Huntington's disease [22,23], and epilepsy [6] (reviewed in [10,24]).…”

Section: Introductionmentioning

confidence: 99%

stim2b Knockout Induces Hyperactivity and Susceptibility to Seizures in Zebrafish Larvae

Wasilewska¹,

Gupta²,

Wojtaś³

et al. 2020

Cells

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In neurons, stromal interaction molecule (STIM) proteins regulate store-operated Ca2+ entry (SOCE) and are involved in calcium signaling pathways. However, STIM activity in neurological diseases is unclear and should be clarified by studies that are performed in vivo rather than in cultured cells in vitro. The present study investigated the role of neuronal Stim2b protein in zebrafish. We generated stim2b knockout zebrafish, which were fertile and had a regular lifespan. Using various behavioral tests, we found that stim2b−/− zebrafish larvae were hyperactive compared with wild-type fish. The mutants exhibited increases in mobility and thigmotaxis and disruptions of phototaxis. They were also more sensitive to pentylenetetrazol and glutamate treatments. Using lightsheet microscopy, a higher average oscillation frequency and higher average amplitude of neuronal Ca2+ oscillations were observed in stim2b−/− larvae. RNA sequencing detected upregulation of the annexin 3a and gpr39 genes and downregulation of the rrm2, neuroguidin, and homer2 genes. The latter gene encodes a protein that is involved in several processes that are involved in Ca2+ homeostasis in neurons, including metabotropic glutamate receptors. We propose that Stim2b deficiency in neurons dysregulates SOCE and triggers changes in gene expression, thereby causing abnormal behavior, such as hyperactivity and susceptibility to seizures.

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“…STIM2.1 is a negative regulator of SOCE, and STIM2.2 is the counterpart of STIM2 (Miederer et al, 2015). Both isoforms are equally expressed in MSNs (Czeredys et al, 2018), but their functions in the regulation of SOCE in neurons are unknown. STIM1 has high affinity for Ca 2+ and requires the higher depletion of Ca 2+ from the ER during SOCE.…”

Section: Neuronal Ca 2+ Signaling Via Store-operated Ca 2+ Channels Umentioning

confidence: 99%

“…It also blocks the inhibitory actions of ankyrin on IP3R3 (Wu and Bowen, 2008 ). In MSNs, where IP3R1 is a predominant neuronal isoform (Czeredys et al, 2018 ) S1R resisting in MAMs and stabilizes IP3R3 (Ryskamp D. A. et al, 2019 ). The S1R directly binds to IP3R1 and leads to the stimulation of protein kinase C (PKC) activity and suppression of IP3 synthesis in hepatocytes (Abou-Lovergne et al, 2011 ).…”

Section: Neuronal Ca 2+ Signaling Via Store-operatmentioning

confidence: 99%

“…IP3R1 is abnormally activated in HD models that dysregulate ER Ca 2+ dynamics. IP3R1 is the main IP3R isoform that is expressed in the striatum (Czeredys et al, 2018 ), and its activity is elevated in YAC128 MSNs (Wu et al, 2016 ). In MSNs, the overexpression of HTT-138Q activates IP3R1 more strongly compared with HTT that contains only 82Q repeats (Tang et al, 2003 ).…”

Section: Ca 2+ Signaling Pathways That May Affect mentioning

confidence: 99%

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Dysregulation of Neuronal Calcium Signaling via Store-Operated Channels in Huntington's Disease

Czeredys

2020

Front. Cell Dev. Biol.

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Huntington's disease (HD) is a progressive neurodegenerative disorder that is characterized by motor, cognitive, and psychiatric problems. It is caused by a polyglutamine expansion in the huntingtin protein that leads to striatal degeneration via the transcriptional dysregulation of several genes, including genes that are involved in the calcium (Ca2+) signalosome. Recent research has shown that one of the major Ca2+ signaling pathways, store-operated Ca2+ entry (SOCE), is significantly elevated in HD. SOCE refers to Ca2+ flow into cells in response to the depletion of endoplasmic reticulum Ca2+ stores. The dysregulation of Ca2+ homeostasis is postulated to be a cause of HD progression because the SOCE pathway is indirectly and abnormally activated by mutant huntingtin (HTT) in γ-aminobutyric acid (GABA)ergic medium spiny neurons (MSNs) from the striatum in HD models before the first symptoms of the disease appear. The present review summarizes recent studies that revealed a relationship between HD pathology and elevations of SOCE in different models of HD, including YAC128 mice (a transgenic model of HD), cellular HD models, and induced pluripotent stem cell (iPSC)-based GABAergic medium spiny neurons (MSNs) that are obtained from adult HD patient fibroblasts. SOCE in MSNs was shown to be mediated by currents through at least two different channel groups, Ca2+ release-activated Ca2+ current (ICRAC) and store-operated Ca2+ current (ISOC), which are composed of stromal interaction molecule (STIM) proteins and Orai or transient receptor potential channel (TRPC) channels. Their role under physiological and pathological conditions in HD are discussed. The role of Huntingtin-associated protein 1 isoform A in elevations of SOCE in HD MSNs and potential compounds that may stabilize elevations of SOCE in HD are also summarized. Evidence is presented that shows that the dysregulation of molecular components of SOCE or pathways upstream of SOCE in HD MSN neurons is a hallmark of HD, and these changes could lead to HD pathology, making them potential therapeutic targets.

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Huntingtin-Associated Protein 1A Regulates Store-Operated Calcium Entry in Medium Spiny Neurons From Transgenic YAC128 Mice, a Model of Huntington’s Disease

Cited by 23 publications

References 60 publications

STIM Proteins and Glutamate Receptors in Neurons: Role in Neuronal Physiology and Neurodegenerative Diseases

STIM Proteins and Glutamate Receptors in Neurons: Role in Neuronal Physiology and Neurodegenerative Diseases

stim2b Knockout Induces Hyperactivity and Susceptibility to Seizures in Zebrafish Larvae

Dysregulation of Neuronal Calcium Signaling via Store-Operated Channels in Huntington's Disease

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