Details

Autor(en) / Beteiligte

• Vogt-Eisele, Angela
• Kruger, Carola
• Duning, Kerstin
• Weber, Daniela
• Spoelgen, Robert
• Pitzer, Claudia
• Plaas, Christian
• Eisenhardt, Gisela
• Meyer, Annette
• Vogt, Gerhard
• Krieger, Markus
• Handwerker, Eva
• Wennmann, Dirk Oliver
• Weide, Thomas
• Skryabin, Boris V
• Klugmann, Matthias
• Pavenstadt, Hermann
• Huentelmann, Matthew J
• Kremerskothen, Joachim
• Schneider, Armin

Titel

KIBRA (KIdney/BRAin protein) regulates learning and memory and stabilizes Protein kinase M[zeta]

Ist Teil von

• Journal of neurochemistry, 2014-03, Vol.128 (5), p.686

Ort / Verlag

New York: Blackwell Publishing Ltd

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• The WWC1 gene has been genetically associated with human episodic memory performance, and its product KIdney/BRAin protein (KIBRA) has been shown to interact with the atypical protein kinase protein kinase M [zeta] (PKM[zeta]). Although recently challenged, PKM[zeta] remains a candidate postsynaptic regulator of memory maintenance. Here, we show that PKM[zeta] is subject to rapid proteasomal degradation and that KIBRA is both necessary and sufficient to counteract this process, thus stabilizing the kinase and maintaining its function for a prolonged time. We define the binding sequence on KIBRA, a short amino acid motif near the C-terminus. Both hippocampal knock-down of KIBRA in rats and KIBRA knock-out in mice result in decreased learning and memory performance in spatial memory tasks supporting the notion that KIBRA is a player in episodic memory. Interestingly, decreased memory performance is accompanied by decreased PKM[zeta] protein levels. We speculate that the stabilization of synaptic PKM[zeta] protein levels by KIBRA may be one mechanism by which KIBRA acts in memory maintenance. KIBRA/WWC1 has been genetically associated with human episodic memory. KIBRA has been shown to be post-synaptically localized, but its function remained obscure. Here, we show that KIBRA shields PKM[zeta], a kinase previously linked to memory maintenance, from proteasomal degradation via direct interaction. KIBRA levels in the rodent hippocampus correlate closely both to spatial memory performance in rodents and to PKM[zeta] levels. Our findings support a role for KIBRA in memory, and unveil a novel function for this protein. [PUBLICATION ABSTRACT]