Abstract
Learning and memory rely on changes in postsynaptic glutamergic a-amino-3-hydroxy-5-methyl-4-isoxazo-lepropionic acid (AMPA)-type receptor (AMPAR) number, spatial organization, and function. The Hippo pathway component WW and C2 domain-containing protein 1 (WWC1) regulates AMPAR surface expression and impacts on memory performance. However, synaptic binding partners of WWC1 and its hierarchical po-sition in AMPAR complexes are largely unclear. Using cell-surface proteomics in hippocampal tissue of Wwc1-deficient mice and by generating a hippocampus-specific interactome, we show that WWC1 is a major regulatory platform in AMPAR signaling networks. Under basal conditions, the Hippo pathway members WWC1 and large tumor-suppressor kinase (LATS) are associated, which might prevent WWC1 effects on synaptic proteins. Reduction of WWC1/LATS binding through a point mutation at WWC1 elevates the abundance of WWC1 in AMPAR complexes and improves hippocampal-dependent learning and memory. Thus, uncoupling of WWC1 from the Hippo pathway to AMPAR-regulatory complexes provides an innovative strategy to enhance synaptic transmission.
Item Type: | Journal article |
---|---|
Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 2211-1247 |
Language: | English |
Item ID: | 112029 |
Date Deposited: | 02. Apr 2024, 07:32 |
Last Modified: | 02. Apr 2024, 07:32 |