Type 1 Inositol Trisphosphate Receptor Regulates Cerebellar Circuits by Maintaining the Spine Morphology of Purkinje Cells in Adult Mice

Sugawara, Takeyuki; Hisatsune, Chihiro; Le, Tung Dinh; Hashikawa, Tsutomu; Hirono, Moritoshi; Hattori, Mitsuharu; Nagao, Soichi; Mikoshiba, Katsuhiko

doi:10.1523/jneurosci.0545-13.2013

Cited by 71 publications

(72 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Behavioral experiments revealed that IP 3 Rs are involved in memory formation; in particular, they are required for long-term memory [47]. Recently, Mikoshiba's research group has shown that the IP 3 R1 in cerebellar PCs plays a crucial role in controlling the maintenance of parallel fiber-PC synaptic circuits in the mature cerebellum in vivo [48]. Also, it has been shown that IP 3 R1, together with other important intracellular proteins, plays a significant role in PC dendritic development [49].…”

Section: Structure Function and Regulation Of Ip 3 Rsmentioning

confidence: 99%

Inositol 1,4,5‐trisphosphate receptors and neurodegenerative disorders

Egorova

Bezprozvanny

2018

The FEBS Journal

View full text Add to dashboard Cite

The inositol 1,4,5-trisphosphate receptor (IP 3 R) is an intracellular ion channel that mediates the release of calcium ions from the endoplasmic reticulum. It plays a role in basic biological functions, such as cell division, differentiation, fertilization and cell death, and is involved in developmental processes including learning, memory and behavior. Deregulation of neuronal calcium signaling results in disturbance of cell homeostasis, synaptic loss and dysfunction, eventually leading to cell death. Three IP 3 R subtypes have been identified in mammalian cells and the predominant isoform in neurons is IP 3 R type 1. Dysfunction of IP 3 R type 1 may play a role in the pathogenesis of certain neurodegenerative diseases as enhanced activity of the IP 3 R was observed in models of Huntington's disease, spinocerebellar ataxias and Alzheimer's disease. These results suggest that IP 3 R-mediated signaling is a potential target for treatment of these disorders. In this review we discuss the structure, functions and regulation of the IP 3 R in healthy neurons and in conditions of neurodegeneration. IntroductionInositol 1,4,5-trisphosphate receptors (IP 3 Rs) are a family of intracellular ion channels that mediate calcium (Ca 2+ ) release from the endoplasmic reticulum (ER) following stimulation by the second messenger inositol 1,4,5-trisphosphate (IP 3 ). Generation of IP 3 molecules is caused by the activation of phospholipase C in response to the activation of G proteincoupled receptors such as serotonergic receptors, adrenergic receptors, calcitonin receptors, histamine receptors, metabotropic glutamate receptors (mGluRs), Abbreviations AAV, adeno-associated virus; AD, Alzheimer's disease; ALG-2, apoptosis-linked gene 2; ARM, armadillo; Ab, beta amyloid; BH, Bcl-2 homology; CaBP1, calcium-binding protein 1; CTD, C-terminal domain; EM, electron microscopy; ER, endoplasmic reticulum; FAD, familial Alzheimer's disease; GRP78, 78-kDa glucose regulated protein; HAP1, huntingtin-associated protein 1; HD, Huntington's disease; HelD, helical domain; Htt, huntingtin; IBC, IP 3 -binding core; IICR, inositol 1,4,5-trisphosphate-induced calcium release; ILD, 'intervening lateral' domain; IP 3 , inositol 1,4,5-trisphosphate; IP 3 R1, IP 3 R type 1; IP 3 R, inositol 1,4,5-trisphosphate receptor; IRBIT, IP 3 R binding protein released with IP 3 ; KO, knock-out; LBD, ligand-binding domain; LNK, helical linker domain; MCI, mild cognitive impairment; mGluR, metabotropic glutamate receptor; mPTP, mitochondrial permeability transition pore; MSN, medium spiny neuron; NMDA, N-methyl-D-aspartate; NTR, Nterminal region; Opt, opisthotonos; PC, Purkinje cell; polyQ, polyglutamine; PS, presenilin; RyR, ryanodine receptor; SAD, sporadic Alzheimer's disease; SCA, spinocerebellar ataxia; SD, IP 3 -binding suppressor domain; SUMF1, sulfatase modifying factor 1; TG2, transglutaminase type 2; TMD, transmembrane domain; WT, wild-type; YAC, yeast artificial chromosome; b-TF, b-trefoil. 3547The (Fig. 1). Upon extracellular stimulation -by various ...

show abstract

Section: Structure Function and Regulation Of Ip 3 Rsmentioning

confidence: 99%

Inositol 1,4,5‐trisphosphate receptors and neurodegenerative disorders

Egorova

Bezprozvanny

2018

The FEBS Journal

View full text Add to dashboard Cite

show abstract

“…However, this modification subsequently would have a chronically negative effect on Ca 2+ signaling, because it is much more static than noncovalent allosteric modulators required for the control of rapid and dynamic Ca 2+ signaling such as Ca 2+ oscillation. Therefore, the TG2-dependent allosteric modulation should chronically set in motion cascades of defective signaling related to pathological states; up-regulation of TG2 may disrupt the IP 3 R1-mediated plasticity of neuronal signaling (3,(10)(11)(12) and the homeostatic control of cellular processes including mitochondria energy production (23), autophagy regulation (24-27), ER stress (28), and others (29)(30)(31) and ultimately increases cellular stress, resulting in further TG2 up-regulation proceeding a vicious cycle. Given the widespread brain expression profiles of TG2 and IP 3 R1, we propose that the mechanism described in this study might potentially serve as a general principle for many other diseases of the brain or other tissues in which TG2 is up-regulated by a disease-initiating agent.…”

Section: Discussionmentioning

confidence: 99%

“…Deletion of the genes encoding the type 1 IP 3 R (IP 3 R1) leads to perturbations in long-term potentiation/ depression (3,10,11) and spinogenesis (12), and the human genetic disease spinocerebellar ataxia 15 is caused by haploinsufficiency of the IP 3 R1 gene (13)(14)(15). Dysregulation of IP 3 R1 is also implicated in neurodegenerative diseases including Huntington disease (HD) (16)(17)(18)) and Alzheimer's disease (AD) (19)(20)(21)(22).…”

mentioning

confidence: 99%

Aberrant calcium signaling by transglutaminase-mediated posttranslational modification of inositol 1,4,5-trisphosphate receptors

Hamada

Terauchi

Nakamura

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The inositol 1,4,5-trisphosphate receptor (IP 3 R) in the endoplasmic reticulum mediates calcium signaling that impinges on intracellular processes. IP 3 Rs are allosteric proteins comprising four subunits that form an ion channel activated by binding of IP 3 at a distance. Defective allostery in IP 3 R is considered crucial to cellular dysfunction, but the specific mechanism remains unknown. Here we demonstrate that a pleiotropic enzyme transglutaminase type 2 targets the allosteric coupling domain of IP 3 R type 1 (IP 3 R1) and negatively regulates IP 3 R1-mediated calcium signaling and autophagy by locking the subunit configurations. The control point of this regulation is the covalent posttranslational modification of the Gln2746 residue that transglutaminase type 2 tethers to the adjacent subunit. Modification of Gln2746 and IP 3 R1 function was observed in Huntington disease models, suggesting a pathological role of this modification in the neurodegenerative disease. Our study reveals that cellular signaling is regulated by a new mode of posttranslational modification that chronically and enzymatically blocks allosteric changes in the ligand-gated channels that relate to disease states.L igand-gated ion channels function by allostery that is the regulation at a distance; the allosteric coupling of ligand binding with channel gating requires reversible changes in subunit configurations and conformations (1). Inositol 1,4,5-trisphosphate receptors (IP 3 Rs) are ligand-gated ion channels that release calcium ions (Ca 2+ ) from the endoplasmic reticulum (ER) (2, 3). IP 3 Rs are allosteric proteins comprising four subunits that assemble a calcium channel with fourfold symmetry about an axis perpendicular to the ER membrane. The subunits of three IP 3 R isoforms (IP 3 R1, IP 3 R2, and IP 3 R3) are structurally divided into three domains: the IP 3 -binding domain (IBD), the regulatory domain, and the channel domain (3-6). Fitting of the IBD X-ray structures (7, 8) to a cryo-EM map (9) indicates that the IBD activates a remote Ca 2+ channel by allostery (8); however, the current X-ray structure only spans 5% of each tetramer, such that the mechanism underlying allosteric coupling of the IBD to channel gating remains unknown.The IP 3 R in the ER mediates intracellular calcium signaling that impinges on homeostatic control in various subsequent intracellular processes. Deletion of the genes encoding the type 1 IP 3 R (IP 3 R1) leads to perturbations in long-term potentiation/ depression (3, 10, 11) and spinogenesis (12), and the human genetic disease spinocerebellar ataxia 15 is caused by haploinsufficiency of the IP 3 R1 gene (13-15). Dysregulation of IP 3 R1 is also implicated in neurodegenerative diseases including Huntington disease (HD) (16-18) and Alzheimer's disease (AD) (19)(20)(21)(22). IP 3 Rs also control fundamental cellular processes-for example, mitochondrial energy production (23, 24), autophagy regulation (24-27), ER stress (28), hepatic gluconeogenesis (29), pancreatic exocytosis (30), and macrophag...

show abstract

“…Images of the same widow were taken 3, 6, and 10 days after the surgery. the deep cerebellar nuclei, and the structural plasticity of Purkinje cell spines has been of great interest (Black et al 1990;Cesa et al 2005Cesa et al , 2007Kleim et al 1998;Lee et al 2007Lee et al , 2013Sdrulla and Linden 2007;Sugawara et al 2013). However, because of the small size and high density of spines, single spines are not reliably resolved in vivo even with two-photon microscopy.…”

Section: Discussionmentioning

confidence: 99%

Long-term in vivo time-lapse imaging of synapse development and plasticity in the cerebellum

Nishiyama

Colonna

Shen

et al. 2014

Journal of Neurophysiology

View full text Add to dashboard Cite

Synapses are continuously formed and eliminated throughout life in the mammalian brain, and emerging evidence suggests that this structural plasticity underlies experience-dependent changes of brain functions such as learning and long-term memory formation. However, it is generally difficult to understand how the rewiring of synaptic circuitry observed in vivo eventually relates to changes in animal's behavior. This is because afferent/efferent connections and local synaptic circuitries are very complicated in most brain regions, hence it is largely unclear how sensorimotor information is conveyed, integrated, and processed through a brain region that is imaged. The cerebellar cortex provides a particularly useful model to challenge this problem because of its simple and welldefined synaptic circuitry. However, owing to the technical difficulty of chronic in vivo imaging in the cerebellum, it remains unclear how cerebellar neurons dynamically change their structures over a long period of time. Here, we showed that the commonly used method for neocortical in vivo imaging was not ideal for long-term imaging of cerebellar neurons, but simple optimization of the procedure significantly improved the success rate and the maximum time window of chronic imaging. The optimized method can be used in both neonatal and adult mice and allows time-lapse imaging of cerebellar neurons for more than 5 mo in ϳ80% of animals. This method allows vital observation of dynamic cellular processes such as developmental refinement of synaptic circuitry as well as long-term changes of neuronal structures in adult cerebellum under longitudinal behavioral manipulations.long-term, time-lapse imaging; two-photon microscopy; development; plasticity IN VIVO TIME-LAPSE MICROSCOPY is now extensively used for imaging fine neuronal structures and activity in the brain of living animals. These experiments have revealed the dynamic nature of synaptic wiring and functional architecture of neuronal ensembles, providing novel insights into experience-dependent changes of brain functions (Bhatt et al. 2009;Chen and Nedivi 2010;Huber et al. 2012). However, it is generally difficult to understand how the formation and elimination of synapses modify the function of local brain circuitry, and eventually, an animal's behavior.The cerebellum provides a unique advantage to challenge this problem. Unlike most other brain regions, extensively characterized anatomical and physiological properties of cerebellar neurons provide testable models regarding how sensorimotor information is conveyed and integrated, and how plas-

show abstract

Type 1 Inositol Trisphosphate Receptor Regulates Cerebellar Circuits by Maintaining the Spine Morphology of Purkinje Cells in Adult Mice

Cited by 71 publications

References 65 publications

Inositol 1,4,5‐trisphosphate receptors and neurodegenerative disorders

Inositol 1,4,5‐trisphosphate receptors and neurodegenerative disorders

Aberrant calcium signaling by transglutaminase-mediated posttranslational modification of inositol 1,4,5-trisphosphate receptors

Long-term in vivo time-lapse imaging of synapse development and plasticity in the cerebellum

Contact Info

Product

Resources

About