WWC1/2 regulate spinogenesis and cognition in mice by stabilizing AMOT

Cao, Runyi; Zhu, Rui; Sha, Zhao; Qi, Sixian; Lei, Yubin; Tan, Yanfeng; Zhu, Yuwen; Wang, Yu; Yu, Fa‐Xing

doi:10.21203/rs.3.rs-2389039/v1

Cited by 3 publications

(4 citation statements)

References 62 publications

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“…Interestingly, mutation of the PICK1 PDZ domain also disrupts PICK1-KIBRA interaction and KIBRA-induced PICK1 clustering. This result could suggest that PICK1 PDZ domain/KIBRA PDZ ligand interactions also contribute to PICK1-KIBRA interaction (86). However, we hypothesize that these data reflect the fact that the PICK1 PDZ and BAR domains can interact, promoting a 'closed' conformation of PICK1 that disrupts BAR domain-dependent interactions (56,58,61,77).…”

Section: Pick1-kibra Interactionmentioning

confidence: 93%

PICK1 links KIBRA and AMPA receptors in coiled-coil-driven supramolecular complexes

Shao,

Volk

2024

Preprint

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The human memory-associated protein KIBRA regulates synaptic plasticity and trafficking of AMPA-type glutamate receptors, and is implicated in multiple neuropsychiatric and cognitive disorders. How KIBRA forms complexes with and regulates AMPA receptors remains unclear. Here, we show that KIBRA does not interact directly with the AMPA receptor subunit GluA2, but that PICK1, a key regulator of AMPA receptor trafficking, can serve as a bridge between KIBRA and GluA2. We identified structural determinants of KIBRA-PICK1-AMPAR complexes by investigating interactions and cellular expression patterns of different combinations of KIBRA and PICK1 domain mutants. We find that the PICK1 BAR domain, a coiled-coil structure, is sufficient for interaction with KIBRA, whereas mutation of the BAR domain disrupts KIBRA-PICK1-GluA2 complex formation. In addition, KIBRA recruits PICK1 into large supramolecular complexes, a process which requires KIBRA coiled-coil domains. These findings reveal molecular mechanisms by which KIBRA can organize key synaptic signaling complexes.

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Section: Pick1-kibra Interactionmentioning

confidence: 93%

PICK1 links KIBRA and AMPA receptors in coiled-coil-driven supramolecular complexes

Shao,

Volk

2024

Preprint

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“…In addition, USP9X functions as a deubiquitinating enzyme for Amot-p130 and Amotl2, which positively regulate the Hippo signaling pathway and enhance LATS kinase to inhibit tumor growth (44). A recent study has found that WWC proteins recruit USP9X stabilization Amot family proteins to regulate spinal cord genesis and cognition (45). Downstream regulation of the Amot family proteins.…”

Section: Post-translational Modifications Of the Amot Family Proteinsmentioning

confidence: 99%

Role of angiomotin family members in human diseases (Review)

Wang,

Ye,

Jin

2024

Exp Ther Med

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Angiomotin (Amot) family members, including Amot, Amot-like protein 1 (Amotl1) and Amot-like protein 2 (Amotl2), have been found to interact with angiostatins. In addition, Amot family members are involved in various physiological and pathological functions such as embryonic development, angiogenesis and tumorigenesis. Some studies have also demonstrated its regulation in signaling pathways such as the Hippo signaling pathway, AMPK signaling pathway and mTOR signaling pathways. Amot family members play an important role in neural stem cell differentiation, dendritic formation and synaptic maturation. In addition, an increasing number of studies have focused on their function in promoting and/or suppressing cancer, but the underlying mechanisms remain to be elucidated. The present review integrated relevant studies on upstream regulation and downstream signals of Amot family members, as well as the latest progress in physiological and pathological functions and clinical applications, hoping to offer important ideas for further research. Contents1. Introduction 2. The structure of Amot family 3. Upstream and downstream regulation of the Amot family proteins 4. The role of Amot family proteins in physiological regulation 5. Role of Amot family proteins in cancer and other disease 6. Clinic application through targeting Amot family proteins 7. Conclusion and future directions

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“…[ 118 ] Recent findings demonstrate that WWC1‐3 directly bind to Motins and recruit ubiquitin‐specific peptidase 9 X‐linked (USP9X) for the deubiquitination and stabilization of Motins. [ 119 ] In mice, neuron‐specific deletion of Wwc1 and Wwc2 reduces Motin expression and dendritic spine density in the cortex and hippocampus, leading to impaired cognitive functions such as memory and learning. Interestingly, ectopic expression of AMOT partially rescues the neuronal phenotype associated with Wwc1/2 deletion.…”

Section: Motins In the Nervous Systemmentioning

confidence: 99%

“…Thus, WWC proteins modulate spinogenesis and cognition by regulating Motin stability. [ 119 ] Therefore, AMOT regulates neuronal development and maturation, and these processes are dependent or independent of YAP/TAZ.…”

Section: Motins In the Nervous Systemmentioning

confidence: 99%

Angiomotin family proteins in the Hippo signaling pathway

Wang,

2024

BioEssays

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The Motin family proteins (Motins) are a class of scaffolding proteins consisting of Angiomotin (AMOT), AMOT‐like protein 1 (AMOTL1), and AMOT‐like protein 2 (AMOTL2). Motins play a pivotal role in angiogenesis, tumorigenesis, and neurogenesis by modulating multiple cellular signaling pathways. Recent findings indicate that Motins are components of the Hippo pathway, a signaling cascade involved in development and cancer. This review discusses how Motins are integrated into the Hippo signaling network, as either upstream regulators or downstream effectors, to modulate cell proliferation and migration. The repression of YAP/TAZ by Motins contributes to growth inhibition, whereas subcellular localization of Motins and their interactions with actin fibers are critical in regulating cell migration. The net effect of Motins on cell proliferation and migration may contribute to their diverse biological functions.

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WWC1/2 regulate spinogenesis and cognition in mice by stabilizing AMOT

Cited by 3 publications

References 62 publications

PICK1 links KIBRA and AMPA receptors in coiled-coil-driven supramolecular complexes

PICK1 links KIBRA and AMPA receptors in coiled-coil-driven supramolecular complexes

Role of angiomotin family members in human diseases (Review)

Angiomotin family proteins in the Hippo signaling pathway

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