1. SYGNIS Bioscience, , Heidelberg, Germany;2. Department of Internal Medicine D, General Internal Medicine and Nephrology, University Hospital of Münster, , Münster, Germany;3. Institute of Experimental Pathology, ZMBE, University of Münster, , Muenster, Germany;4. Interdisciplinary Center for Clinical Research (IZKF), University of Muenster, , Muenster, Germany;5. Department Functional Genomics, University of New‐South Wales, , Sydney, NSW, Australia;6. The Translational Genomics Research Institute, Neurogenomics Division, , Phoenix, Arizona, USA
Abstract:
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 ζ (PKMζ). Although recently challenged, PKMζ remains a candidate postsynaptic regulator of memory maintenance. Here, we show that PKMζ 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 PKMζ protein levels. We speculate that the stabilization of synaptic PKMζ protein levels by KIBRA may be one mechanism by which KIBRA acts in memory maintenance.
