Dendritic spine morphology and memory formation depend on postsynaptic Caskin proteins
| Autor: | Metta Dülk, Anna Fekete, Sándor Borbély, Attila Szűcs, Virág Vas, Szabolcs Pesti, Katalin Schlett, Szilvia Pusztai, Norbert Bencsik, László Buday, Viktor Kis |
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| Přispěvatelé: | MTA-ELTE-NAP B Molekuláris és Rendszer Neurobiológiai Kutatócsoport, Élettani és Neurobiológiai Tanszék, MTA-ELTE-NAP B Idegi Sejtbiológia Kutatócsoport, Kísérletes Állattani Osztály, Orvosi Vegytani, Molekuláris Biológiai és Patobiokémiai Intézet, Sejtbiológia és Molekuláris Medicina Tanszék, Enzim_400, Jelátviteli és Funkcionális Genomika Kutatócsoport (Lendület), Részecske- és Magfizikai Intézet, Rácz Károly Doktori Iskola, Enzimológiai Intézet, MTA-ELTE Molekuláris és Rendszer Neurobiológiai Kutatócsoport, Balatoni Limnológiai Intézet, Celluláris Idegélettani Kutatócsoport, Biológia Doktori Iskola, MTA Természettudományi Kutatóközpont, Doktori Iskola, MTA-TTK-NAP B Alvási Oszcillációk Kutatócsoport, Anatómiai, Sejt- és Fejlődésbiológiai Tanszék |
| Rok vydání: | 2019 |
| Předmět: |
Scaffold protein
Dendritic spine Dendritic Spines Primary Cell Culture Spatial Learning lcsh:Medicine Nerve Tissue Proteins AMPA receptor Hippocampal formation Hippocampus Article Mice Postsynaptic potential LTP induction Animals Receptors AMPA lcsh:Science Cells Cultured Embryonic Stem Cells Adaptor Proteins Signal Transducing Spatial Memory Mice Knockout Multidisciplinary Chemistry lcsh:R Long-term potentiation Spine plasticity Cell biology nervous system lcsh:Q Postsynaptic density |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-16 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | CASK-interactive proteins, Caskin1 and Caskin2, are multidomain neuronal scaffold proteins. Recent data from Caskin1 knockout animals indicated only a mild role of Caskin1 in anxiety and pain perception. In this work, we show that deletion of both Caskins leads to severe deficits in novelty recognition and spatial memory. Ultrastructural analyses revealed a reduction in synaptic profiles and dendritic spine areas of CA1 hippocampal pyramidal neurons of double knockout mice. Loss of Caskin proteins impaired LTP induction in hippocampal slices, while miniature EPSCs in dissociated hippocampal cultures appeared to be unaffected. In cultured Caskin knockout hippocampal neurons, overexpressed Caskin1 was enriched in dendritic spine heads and increased the amount of mushroom-shaped dendritic spines. Chemically induced LTP (cLTP) mediated enlargement of spine heads was augmented in the knockout mice and was not influenced by Caskin1. Immunocytochemistry and immunoprecipitation confirmed that Shank2, a master scaffold of the postsynaptic density, and Caskin1 co-localized within the same complex. Phosphorylation of AMPA receptors was specifically altered by Caskin deficiency and was not elevated by cLTP treatment further. Taken together, our results prove a previously unnoticed postsynaptic role of Caskin scaffold proteins and indicate that Caskins influence learning abilities via regulating spine morphology and AMPA receptor localisation. |
| Databáze: | OpenAIRE |
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