Hippocalcin Functions as a Calcium Sensor in Hippocampal LTD

Palmer, Claire L.; Lim, Wonil; Hastie, Peter G.R.; Toward, Marie Ann; Korolchuk, Viktor I.; Burbidge, Stephen A.; Banting, George; Collingridge, Graham L.; Isaac, John T.R.; Henley, Jeremy M.

doi:10.1016/j.neuron.2005.06.014

Cited by 125 publications

(137 citation statements)

References 39 publications

Supporting

Mentioning

134

Contrasting

Order By: Relevance

“…Hippocalcin protects cells against endoplasmic reticulum stress-induced cell death and functions as a calcium sensor in synaptic plasticity. 38,39 Furthermore, 26 of the proteins that were highly ubiquitylated after ischemia and trapped in Triton X-100-insoluble aggregates have a role in long-term potentiation. It is therefore reasonable to conclude that the postischemic accumulation of ubiquitylated proteins in insoluble aggregates contributes to the pathologic process induced by transient cerebral ischemia and results in impaired endoplasmic reticulum function, suppression of protein synthesis, and impairment of neuronal functions associated with learning and memory.…”

Section: Proteomics Of Postischemic Ubiquitin Aggregates M Iwabuchi Ementioning

confidence: 99%

Characterization of the Ubiquitin-Modified Proteome Regulated by Transient Forebrain Ischemia

Iseki

Sheng

Thompson³

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Ubiquitylation is a posttranslational protein modification that modulates various cellular processes of key significance, including protein degradation and DNA damage repair. In animals subjected to transient cerebral ischemia, ubiquitin-conjugated proteins accumulate in Triton-insoluble aggregates. Although this process is widely considered to modulate the fate of postischemic neurons, few attempts have been made to characterize the ubiquitin-modified proteome in these aggregates. We performed proteomics analyses to identify ubiquitylated proteins in postischemic aggregates. Mice were subjected to 10 minutes of forebrain ischemia and 4 hours of reperfusion. The hippocampi were dissected, aggregates were isolated, and trypsin-digested after spiking with GG-BSA as internal standard. K-e-GG-containing peptides were immunoprecipitated and analyzed by label-free quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. We identified 1,664 peptides to 520 proteins containing at least one K-e-GG. Sixty-six proteins were highly ubiquitylated, with 10 or more K-e-GG peptides. Based on selection criteria of greater than fivefold increase and Po0.001, 763 peptides to 272 proteins were highly enriched in postischemic aggregates. These included proteins involved in important neuronal functions and signaling pathways that are impaired after ischemia. Results of this study could serve as an important platform to uncover the mechanisms linking insoluble ubiquitin aggregates to the functions of postischemic neurons.

show abstract

Section: Proteomics Of Postischemic Ubiquitin Aggregates M Iwabuchi Ementioning

confidence: 99%

Characterization of the Ubiquitin-Modified Proteome Regulated by Transient Forebrain Ischemia

Iseki

Sheng

Thompson³

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…Another Ca 2+ -sensitive protein that has been shown to be involved in synaptic plasticity is hippocalcin 15 , a member of the NCS family that is highly expressed in the hippocampus 29 . The role of hippocalcin can be explored using a well characterised dominant negative (GST-Hip 2-72 ), which is an N-terminal truncation that lacks the Ca 2+ binding sites 15 . As shown in Fig.…”

Section: Hippocalcin Is Involved In Cch-and Syn-machr-ltd Nmentioning

confidence: 99%

“…Since hippocalcin interacts with the clathrin adaptor protein AP2 15 and since AP2 is involved in the internalisation of NMDARs, where it might compete with PSD-95 30 , we investigated the interactions of these three molecules with NMDAR subunits, using co-immunoprecipitation (co-IP) assays (Fig. 6a).…”

Section: Psd-95mentioning

confidence: 99%

“…Antibodies and immunoblotting. Anti-hippocalcin antibody was described previously 15 , and anti-GST antiserum was raised by immunizing a rabbit with purified GST protein. Surface expression of NMDA receptors.…”

Section: Authors Contributionsmentioning

confidence: 99%

“…This process is triggered by a protein phosphatase cascade, involving PP2B and PP1 11,12 , and also involves activation of kinases, such as glycogen synthase kinase-3 13,14 , the membrane targeting of the high affinity neuronal calcium sensor (NCS) protein hippocalcin 15 and alterations in MAGUK proteins, in particular PSD-95 16,17 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Muscarinic receptors induce LTD of NMDAR EPSCs via a mechanism involving hippocalcin, AP2 and PSD-95

et al. 2010

View full text Add to dashboard Cite

Real‐Time, Non‐Invasive Monitoring of Neuronal Differentiation Using Intein‐Enabled Fluorescence Signal Translocation in Genetically Encoded Stem Cell‐Based Biosensors

Lee,

Choi,

Kwon

et al. 2024

Adv Funct Materials

View full text Add to dashboard Cite

Real‐time and non‐invasive monitoring of neuronal differentiation helps to increase understanding of neuronal development and develop stem cell therapies for neurodegenerative diseases. Conventional methods such as RT‐PCR, western blotting, and immunofluorescence (IF), lack single‐cell‐level resolution and require invasive procedures, fixation, and staining. These limitations hinder accurate monitoring progress of neural stem cell (NSC) differentiation and understanding its functions. Herein, a novel approach is reported to non‐invasively monitor neuronal differentiation in real‐time using cell‐based biosensors (CBBs) that detects hippocalcin, biomarker of neuronal differentiation. To construct the hippocalcin sensor proteins, two different hippocalcin bioreceptors are fused to each split‐intein, carrying split‐nuclear localization signal (NLS) peptides, respectively, and fluorescent protein is introduced as reporter. CBBs operated in the presence of hippocalcin to generate functional signal peptides, which promptly translocated the fluorescence signal to the nucleus. The NSC‐based biosensor shows fluorescence signal translocation only upon neuronal differentiation and not undifferentiated stem cells or glial cells. Furthermore, this approach allows monitoring of neural differentiation at earlier stages than detected using IF staining. It is believed that novel CBBs offer an alternative to current techniques by capturing the dynamics of differentiation progress at the single‐cell‐level and providing a tool to evaluate how NSCs efficiently differentiate into neurons.

show abstract

Hippocalcin Functions as a Calcium Sensor in Hippocampal LTD

Cited by 125 publications

References 39 publications

Characterization of the Ubiquitin-Modified Proteome Regulated by Transient Forebrain Ischemia

Characterization of the Ubiquitin-Modified Proteome Regulated by Transient Forebrain Ischemia

Muscarinic receptors induce LTD of NMDAR EPSCs via a mechanism involving hippocalcin, AP2 and PSD-95

Real‐Time, Non‐Invasive Monitoring of Neuronal Differentiation Using Intein‐Enabled Fluorescence Signal Translocation in Genetically Encoded Stem Cell‐Based Biosensors

Contact Info

Product

Resources

About