KIBRA regulates activity-induced AMPA receptor expression and synaptic plasticity in an age-dependent manner

Mendoza, Matthew L.; Quigley, Lilyana; Dunham, Thomas; Volk, Lenora J.

doi:10.1016/j.isci.2022.105623

Cited by 12 publications

(40 citation statements)

References 82 publications

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“…Moreover, aging is thought to cause cognitive decline, which could be explained by changes in age-dependent synaptic plasticity or cellular alterations directly affecting plasticity mechanisms [ 174 , 175 ]. Lik-Wei Wong et al report that the p75 neurotrophin receptor (p75NTR) may represent an important therapeutic target for limiting age-related deficits in memory and cognitive function [ 176 ].…”

Section: Discussionmentioning

confidence: 99%

Advances in the Electrophysiological Recordings of Long-Term Potentiation

Jiang

Bello

Gao

et al. 2023

IJMS

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Understanding neuronal firing patterns and long-term potentiation (LTP) induction in studying learning, memory, and neurological diseases is critical. However, recently, despite the rapid advancement in neuroscience, we are still constrained by the experimental design, detection tools for exploring the mechanisms and pathways involved in LTP induction, and detection ability of neuronal action potentiation signals. This review will reiterate LTP-related electrophysiological recordings in the mammalian brain for nearly 50 years and explain how excitatory and inhibitory neural LTP results have been detected and described by field- and single-cell potentials, respectively. Furthermore, we focus on describing the classic model of LTP of inhibition and discuss the inhibitory neuron activity when excitatory neurons are activated to induce LTP. Finally, we propose recording excitatory and inhibitory neurons under the same experimental conditions by combining various electrophysiological technologies and novel design suggestions for future research. We discussed different types of synaptic plasticity, and the potential of astrocytes to induce LTP also deserves to be explored in the future.

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Section: Discussionmentioning

confidence: 99%

Advances in the Electrophysiological Recordings of Long-Term Potentiation

Jiang

Bello

Gao

et al. 2023

IJMS

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“…We examined WWC2 subcellular localization via serial fractionation in hippocampal tissue 21,36 . WWC2 is present in the cytosol and plasma membrane/crude synaptosome fraction (P2), and is depleted from the purified excitatory PSD (Fig.…”

Section: Wwc2 Interacts With the Inhibitory Postsynaptic Scaffold Gep...mentioning

confidence: 99%

Modulation of GABA_Areceptor trafficking by WWC2 reveals class-specific mechanisms of synapse regulation by WWC family proteins

Dunham,

Wilkerson,

Johnson

et al. 2024

Preprint

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WWC2 (WW and C2 domain-containing protein) is implicated in several neurological disorders, however its function in the brain has yet to be determined. Here, we demonstrate that WWC2 interacts with inhibitory but not excitatory postsynaptic scaffolds, consistent with prior proteomic identification of WWC2 as a putative component of the inhibitory postsynaptic density. Using mice lacking WWC2 expression in excitatory forebrain neurons, we show that WWC2 suppresses GABAAR incorporation into the plasma membrane and regulates HAP1 and GRIP1, which form a complex promoting GABAAR recycling to the membrane. Inhibitory synaptic transmission is dysregulated in CA1 pyramidal cells lacking WWC2. Furthermore, unlike the WWC2 homolog KIBRA (WWC1), a key regulator of AMPA receptor trafficking at excitatory synapses, deletion of WWC2 does not affect synaptic AMPAR expression. In contrast, loss of KIBRA does not affect GABAAR membrane expression. These data reveal unique, synapse class-selective functions for WWC proteins as regulators of ionotropic neurotransmitter receptors and provide insight into mechanisms regulating GABAAR membrane expression.

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“…Previous studies have established the involvement of the WW and C2 domain-containing 1 protein (WWC1, also referred to as KIBRA) in the regulation of AMPAR and its impact on learning and memory in mice (4,(7)(8)(9)(10)(11)(12)(13). Papassotiropoulos et al's genetic association study played a pioneering role in establishing the importance of WWC1 in human memory, highlighting its association with memory performance through various polymorphisms in numerous human studies (14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

“…9 german cancer consortium (DKtK), 80336 Munich, germany. 10 german cancer center (DKFZ), 69120 heidelberg, germany. 11 Research group neurobiology of Stress Resilience, Max Planck institute of Psychiatry, 80804 Munich, germany.…”

Section: Introductionmentioning

confidence: 99%

Inhibiting Hippo pathway kinases releases WWC1 to promote AMPAR-dependent synaptic plasticity and long-term memory in mice

Stepan,

Heinz,

Dethloff

et al. 2024

Sci. Signal.

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The localization, number, and function of postsynaptic AMPA-type glutamate receptors (AMPARs) are crucial for synaptic plasticity, a cellular correlate for learning and memory. The Hippo pathway member WWC1 is an important component of AMPAR-containing protein complexes. However, the availability of WWC1 is constrained by its interaction with the Hippo pathway kinases LATS1 and LATS2 (LATS1/2). Here, we explored the biochemical regulation of this interaction and found that it is pharmacologically targetable in vivo. In primary hippocampal neurons, phosphorylation of LATS1/2 by the upstream kinases MST1 and MST2 (MST1/2) enhanced the interaction between WWC1 and LATS1/2, which sequestered WWC1. Pharmacologically inhibiting MST1/2 in male mice and in human brain-derived organoids promoted the dissociation of WWC1 from LATS1/2, leading to an increase in WWC1 in AMPAR-containing complexes. MST1/2 inhibition enhanced synaptic transmission in mouse hippocampal brain slices and improved cognition in healthy male mice and in male mouse models of Alzheimer’s disease and aging. Thus, compounds that disrupt the interaction between WWC1 and LATS1/2 might be explored for development as cognitive enhancers.

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KIBRA regulates activity-induced AMPA receptor expression and synaptic plasticity in an age-dependent manner

Cited by 12 publications

References 82 publications

Advances in the Electrophysiological Recordings of Long-Term Potentiation

Advances in the Electrophysiological Recordings of Long-Term Potentiation

Modulation of GABA_Areceptor trafficking by WWC2 reveals class-specific mechanisms of synapse regulation by WWC family proteins

Inhibiting Hippo pathway kinases releases WWC1 to promote AMPAR-dependent synaptic plasticity and long-term memory in mice

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KIBRA regulates activity-induced AMPA receptor expression and synaptic plasticity in an age-dependent manner

Cited by 12 publications

References 82 publications

Advances in the Electrophysiological Recordings of Long-Term Potentiation

Advances in the Electrophysiological Recordings of Long-Term Potentiation

Modulation of GABAAreceptor trafficking by WWC2 reveals class-specific mechanisms of synapse regulation by WWC family proteins

Inhibiting Hippo pathway kinases releases WWC1 to promote AMPAR-dependent synaptic plasticity and long-term memory in mice

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Modulation of GABA_Areceptor trafficking by WWC2 reveals class-specific mechanisms of synapse regulation by WWC family proteins