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Cited by 144Neuroscience and Neuropharmacology ResearchCellular transport and secretionGenetics and Neurodevelopmental Disorders

Hippocalcin functions as a calcium sensor in hippocampal LTD.

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Palmer, Claire L., Lim, Wonil, Hastie, Peter G.R., Toward, Marie, Korolchuk, Viktor I., Burbidge, Stephen A., Banting, George, Collingridge, Graham L. +2 more·2005·Neuron
DOI 10.1016/j.neuron.2005.06.014PMC PMC1563146
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Abstract

It is not fully understood how NMDAR-dependent LTD causes Ca(2+)-dependent endocytosis of AMPARs. Here we show that the neuronal Ca(2+) sensor hippocalcin binds the beta2-adaptin subunit of the AP2 adaptor complex and that along with GluR2 these coimmunoprecipitate in a Ca(2+)-sensitive manner. Infusion of a truncated mutant of hippocalcin (HIP(2-72)) that lacks the Ca(2+) binding domains prevents synaptically evoked LTD but has no effect on LTP. These data indicate that the AP2-hippocalcin complex acts as a Ca(2+) sensor that couples NMDAR-dependent activation to regulated endocytosis of AMPARs during LTD.

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  • Hippocalcin binds calcium as well as AP2 (β2 adaptin) and is translocated to the synaptic plasma membrane via the calcium-myristoyl switch to mediate NMDAR-dependent AMPAR endocytosis during LTD.

    “Hippocalcin, which binds calcium as well as AP2 (β2 adaptin), is translocated to the synaptic plasma membrane via the calcium-myristoyl switch to mediate NMDAR-dependent AMPAR endocytosis during LTD [52].”

    From Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD (2009) · cites this paper as [52]

    The Introduction describes hippocalcin as a calcium-binding protein with a Ca2+/myristoyl switch that permits membrane translocation. The Results and Discussion report binding to AP2’s β2-adaptin subunit and support a role in NMDAR-dependent AMPAR endocytosis during LTD. However, the paper reports calcium-dependent enrichment in postsynaptic-density fractions and suggests that the interaction may occur at the plasma membrane; it does not establish translocation specifically to the synaptic plasma membrane as stated. (LLM, conf=0.84)

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Research works printed but not linked: 38

  1. Banbury DN Oakley JD Sessions RB Banting G Tyrphostin A23 inhibits internalization of the transferrin receptor by perturbing the interaction between tyrosine motifs and the medium chain subunit of the AP-2 adaptor complex J. Biol. Chem 2003 278 12022 12028 12556528
  2. Boehm M Bonifacino JS Adaptins: the final recount Mol. Biol. Cell 2001 12 2907 2920 11598180 PMC60144
  3. Carlin RK Grab DJ Cohen RS Siekevitz P Isolation and characterization of postsynaptic densities from various brain regions: enrichment of different types of postsynaptic densities J. Cell Biol 1980 86 831 845 7410481 PMC2110694
  4. Carroll RC Beattie EC Xia H Luscher C Altschuler Y Nicoll RA Malenka RC von Zastrow M Dynamin-dependent endocytosis of ionotropic glutamate receptors Proc. Natl. Acad. Sci. USA 1999 96 14112 14117 10570207 PMC24199
  5. Chapman ER Desai RC Davis AF Tornehl CK Delineation of the oligomerization, AP-2 binding, and synprint binding region of the C2B domain of synaptotagmin J. Biol. Chem 1998 273 32966 32972 9830048
  6. Cottrell JR Borok E Horvath TL Nedivi E CPG2: a brain- and synapse-specific protein that regulates the endocytosis of glutamate receptors Neuron 2004 44 677 690 15541315 PMC3065105
  7. Cupers P Veithen A Hoekstra D Baudhuin P Courtoy PJ Three unrelated perturbations similarly uncouple fluid, bulk-membrane, and receptor endosomal flow in rat fetal fibroblasts Biochem. Biophys. Res. Commun 1997 236 661 664 9245709
  8. Gray EG Whittaker VP The isolation of nerve endings from brain: An electron-microscopic study of cell fragments derived by homogenisation and centrifugation J. Anat 1962 96 79 88 13901297 PMC1244174
  9. Haucke V Wenk MR Chapman ER Farsad K De Camilli P Dual interaction of synaptotagmin with mu2- and alpha-adaptin facilitates clathrin-coated pit nucleation EMBO J 2000 19 6011 6019 11080148 PMC305843
  10. Hirbec H Francis JC Lauri SE Braithwaite SP Coussen F Mulle C Dev KK Coutinho V Meyer G Isaac JT Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP Neuron 2003 37 625 638 12597860 PMC3314502
  11. Hyun JK Yon C Kim YS Noh DY Lee KH Han JS Role of hippocalcin in Ca2+-induced activation of phospholipase D Mol. Cells 2000 10 669 677 11211872
  12. Ivings L Pennington SR Jenkins R Weiss JL Burgoyne RD Identification of Ca2+-dependent binding partners for the neuronal calcium sensor protein neurocalcin delta: interaction with actin, clathrin and tubulin Biochem. J 2002 363 599 608 11964161 PMC1222513
  13. Jarousse N Kelly RB The AP2 binding site of synaptotagmin 1 is not an internalization signal but a regulator of endocytosis J. Cell Biol 2001 154 857 866 11502761 PMC2196445
  14. Kajimoto Y Shirai Y Mukai H Kuno T Tanaka C Molecular cloning of two additional members of the neural visininlike Ca(2+)-binding protein gene family J. Neurochem 1993 61 1091 1096 8360675
  15. Kobayashi M Takamatsu K Saitoh S Miura M Noguchi T Molecular cloning of hippocalcin, a novel calcium-binding protein of the recoverin family exclusively expressed in hippocampus Biochem. Biophys. Res. Commun 1993a 196 1017 8240319
  16. Kobayashi M Takamatsu K Saitoh S Noguchi T Myristoylation of hippocalcin is linked to its calcium-dependent membrane association properties J. Biol. Chem 1993b 268 18898 18904 8360179
  17. Korolchuk VI Banting G CK2 and GAK/auxilin2 are major protein kinases in clathrin-coated vesicles Traffic 2002 3 428 439 12010461
  18. Lee SH Liu L Wang YT Sheng M Clathrin adaptor AP2 and NSF interact with overlapping sites of GluR2 and play distinct roles in AMPA receptor trafficking and hippocampal LTD Neuron 2002 36 661 674 12441055
  19. Luthi A Chittajallu R Duprat F Palmer MJ Benke TA Kidd FL Henley JM Isaac JT Collingridge GL Hippocampal LTD expression involves a pool of AMPARs regulated by the NSF-GluR2 interaction Neuron 1999 24 389 399 10571232
  20. Man HY Lin JW Ju WH Ahmadian G Liu L Becker LE Sheng M Wang YT Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization Neuron 2000 25 649 662 10774732
  21. Marks B McMahon HT Calcium triggers calcineur independent synaptic vesicle recycling in mammalian nerve terminals Curr. Biol 1998 8 740 749 9651678
  22. McMahon HT Mills IG COP and clathrin-coated vesicle budding: different pathways, common approaches Curr. Opin. Cell Biol 2004 16 379 391 15261670
  23. Mercer EA Korhonen L Skoglosa Y Olsson PA Kukkonen JP Lindholm D NAIP interacts with hippocalcin and protects neurons against calcium-induced cell death through cas-pase-3-dependent and -independent pathways EMBO J 2000 19 3597 3607 10899114 PMC313967
  24. Mizuno T Kanazawa I Sakurai M Differential induction of LTP and LTD is not determined solely by instantaneous calcium concentration: an essential involvement of a temporal factor Eur. J. Neurosci 2001 14 701 708 11556894
  25. Mulkey RM Endo S Shenolikar S Malenka RC Involvement of a calcineurin/inhibitor-1 phosphatase cascade in hippocampal long-term depression Nature 1994 369 486 488 7515479
  26. Nagata K Puls A Futter C Aspenstrom P Schaefer E Nakata T Hirokawa N Hall A The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily motor KIF3 EMBO J 1998 17 149 158 9427749 PMC1170366
  27. Nishimune A Nash SR Nakanishi S Henley JM Detection of protein-protein interactions in the nervous system using the two-hybrid system Trends Neurosci 1996 19 261 266 8799967
  28. Nishimune A Isaac JTR Molnar E Noel J Nash SR Tagaya M Collingridge GL Nakanishi S Henley JM NSF binding to GluR2 regulates synaptic transmission Neuron 1998 21 87 97 9697854
  29. Nong Y Huang YQ Salter MW NMDA receptors are movin’ in Curr. Opin. Neurobiol 2004 14 353 361 15194116
  30. O’Callaghan DW Tepikin AV Burgoyne RD Dynamics and calcium sensitivity of the Ca2+/myristoyl switch protein hippocalcin in living cells J. Cell Biol 2003 163 715 721 14638856 PMC2173692
  31. Osterweil E Wells DG Mooseker MS A role for myosin VI in postsynaptic structure and glutamate receptor endocytosis J. Cell Biol 2005 168 329 338 15657400 PMC2171578
  32. Owen DJ Collins BM Evans PR Adaptors for clathrin coats: structure and function Annu. Rev. Cell Dev. Biol 2004 20 153 191 15473838
  33. Palmer CL Cotton L Henley JM The molecular pharmacology and cell biology of {alpha}-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors Pharmacol. Rev 2005 57 253 277 15914469 PMC3314513
  34. Perestenko P Ashby MC Henley JM Real-time imaging of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptor) movements in neurons Biochem. Soc. Trans 2003 31 880 884 12887326 PMC3310154
  35. Saitoh S Takamatsu K Kobayashi M Noguchi T Distribution of hippocalcin mRNA and immunoreactivity in rat brain Neurosci. Lett 1993 157 107 110 8233019
  36. Staudinger J Zhou J Burgess R Elledge SJ Olson EN PICK1: a perinuclear binding protein and substrate for protein kinase C isolated by the yeast two-hybrid system J. Cell Biol 1995 128 263 271 7844141 PMC2120344
  37. Warren RA Green FA Stenberg PE Enns CA Distinct saturable pathways for the endocytosis of different tyrosine motifs J. Biol. Chem 1998 273 17056 17063 9642270
  38. Wu HY Yuen EY Lu YF Matsushita M Matsui H Yan Z Tomizawa K Regulation of N-methyl-D-aspartate receptors by calpain in cortical neurons J. Biol. Chem 2005 280 21588 21593 15790561

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Authors
Palmer, C. L., Lim, W., Hastie, P. G. R., Toward, M., Korolchuk, V. I., Burbidge, S. A., Banting, G., Collingridge, G. L., Isaac, J. T. R., & Henley, J. M.
Affiliations
  • University of Bristol (GB)
  • GlaxoSmithKline (United Kingdom) (GB)
  • National Institutes of Health (US)
Corresponding author
Henley, Jeremy M.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2005-08
Volume
47
Issue
4
Pages
487-494
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2005.06.014
PMC
PMC1563146
OpenAlex
W2034243446
Cited by
144
References
2
Citations by year
2026: 4 · 2025: 4 · 2024: 2 · 2022: 3 · 2021: 10 · 2020: 9 · 2019: 10 · 2018: 5 · 2017: 5 · 2016: 8 · 2015: 6 · 2014: 8 · 2013: 4 · 2012: 13
FWCI
2.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • Research Output (Edinburgh Napier University) (submittedVersion)
  • Edinburgh Napier Research Repository (Edinburgh Napier University) (submittedVersion)
  • Bristol Research (University of Bristol) (submittedVersion)
  • Explore Bristol Research (submittedVersion)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
Wellcome Trust (02089, 059917)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
hippocalcin, calcium sensor, AMPA receptor endocytosis, AP2 adaptor complex, GluR2, calcium-binding domain, long-term potentiation, synaptic plasticity
MeSH terms
Animals, Calcium, Calcium-Binding Proteins, HeLa Cells, Hippocampus, Humans, Nerve Tissue Proteins, Organ Culture Techniques, Receptors, N-Methyl-D-Aspartate, Protein Structure, Tertiary, Receptors, AMPA, Calcium Signaling, Adaptor Protein Complex 2, Adaptor Protein Complex beta Subunits, Long-Term Synaptic Depression, Rats, Hippocalcin

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