Regulation of the interaction between the neuronal <scp>BIN</scp>1 isoform 1 and Tau proteins – role of the <scp>SH</scp>3 domain

Malki, Idir; Cantrelle, François-Xavier; Sottejeau, Yoann; Lippens, Guy; Lambert, Jean‐Charles; Landrieu, Isabelle

doi:10.1111/febs.14185

Cited by 36 publications

(46 citation statements)

References 37 publications

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“…The expression of different isoforms of BIN1 in different tissues remains controversial. The general view is that BIN1 protein isoforms 1‐7 are expressed in the brain; isoform 8 is expressed in the muscle, and isoforms 9 and 10 are ubiquitously expressed . A C‐terminal Src‐homology‐3 (SH‐3) domain, which is encoded by exons 19 and 20, is expressed in all isoforms.…”

Section: Bridging Integratormentioning

confidence: 99%

“…The SH‐3 domain mediates interactions with numerous proteins, such as dynamin 2 . In addition, there are intramolecular interactions with other domains; the reduced mobility of the BIN1‐SH3 domain in the context of BIN1 isoform 1 is caused by the involvement of intramolecular interactions with clathrin and AP‐2 binding (CLAP) domain (334‐376), whereas this domain has significant mobility in the context of BIN1 isoform 9 …”

Section: Bridging Integratormentioning

confidence: 99%

“…Altered splicing may account for myotonic dystrophies, and germline mutations cause congenital centronuclear myopathy . In the progression of AD, the global pattern of expression among BIN1 isoforms may differ; at the protein level, in the brain of an AD patient, BIN1 isoform 1 was reported to decrease, whereas it was reported that there was an increase in the BIN1 isoform 9 . In addition, BIN1 expression increased in the peripheral blood of AD patients, and altered expression has also been observed in transgenic mouse models of AD …”

Section: Bridging Integratormentioning

confidence: 99%

“…The general view is that BIN1 protein isoforms 1-7 are expressed in the brain; isoform 8 is expressed in the muscle, and isoforms 9 and 10 are ubiquitously expressed. 22 A C-terminal Src-homology-3 (SH-3) domain, which is encoded by exons 19 and 20, is expressed in all isoforms. The SH-3 domain mediates interactions with numerous proteins, such as dynamin 2.…”

Section: The Structure Of Bin1mentioning

confidence: 99%

“…23 In addition, there are intramolecular interactions with other domains; the reduced mobility of the BIN1-SH3 domain in the context of BIN1 isoform 1 is caused by the involvement of intramolecular interactions with clathrin and AP-2 binding (CLAP) domain (334-376), whereas this domain has significant mobility in the context of BIN1 isoform 9. 22 The myc-binding domain is encoded by exons 17 and 18 and binds to the c-Myc transcription factor and regulates its function. 24 For example, BIN1 can reverse PD-L1-mediated immune escape by inactivating c-Myc and the EGFR/MAPK signalling pathway in non-small cell lung cancer.…”

Section: The Structure Of Bin1mentioning

confidence: 99%

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Effect of BIN1 on cardiac dysfunction and malignant arrhythmias

et al. 2019

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Heart failure (HF) is the end‐stage syndrome for most cardiac diseases, and the 5‐year morbidity and mortality of HF remain high. Malignant arrhythmia is the main cause of sudden death in the progression of HF. Recently, bridging integrator 1 (BIN1) was discovered as a regulator of transverse tubule function and calcium signalling in cardiomyocytes. BIN1 downregulation is linked to abnormal cardiac contraction, and it increases the possibility of malignant arrhythmias preceding HF. Because of the detectability of cardiac BIN1 in peripheral blood, BIN1 may serve as a predictor of HF and may be useful in therapy development. However, the mechanism of BIN1 downregulation in HF and how BIN1 regulates normal cardiac function under physiological conditions remain unclear. In this review, recent progress in the biological studies of BIN1‐related cardiomyocytes and the effect of cardiac dysfunction and malignant arrhythmia will be discussed.

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Section: Bridging Integratormentioning

confidence: 99%

Section: Bridging Integratormentioning

confidence: 99%

Section: Bridging Integratormentioning

confidence: 99%

Section: The Structure Of Bin1mentioning

confidence: 99%

Section: The Structure Of Bin1mentioning

confidence: 99%

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Effect of BIN1 on cardiac dysfunction and malignant arrhythmias

et al. 2019

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The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis?

Dourlen¹,

et al. 2019

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A strong genetic predisposition (60–80% of attributable risk) is present in Alzheimer’s disease (AD). In view of this major genetic component, identification of the genetic risk factors has been a major objective in the AD field with the ultimate aim to better understand the pathological processes. In this review, we present how the genetic risk factors are involved in APP metabolism, β-amyloid peptide production, degradation, aggregation and toxicity, innate immunity, and Tau toxicity. In addition, on the basis of the new genetic landscape, resulting from the recent high-throughput genomic approaches and emerging neurobiological information, we propose an over-arching model in which the focal adhesion pathway and the related cell signalling are key elements in AD pathogenesis. The core of the focal adhesion pathway links the physiological functions of amyloid precursor protein and Tau with the pathophysiological processes they are involved in. This model includes several entry points, fitting with the different origins for the disease, and supports the notion that dysregulation of synaptic plasticity is a central node in AD. Notably, our interpretation of the latest data from genome wide association studies complements other hypotheses already developed in the AD field, i.e., amyloid cascade, cellular phase or propagation hypotheses. Genetically driven synaptic failure hypothesis will need to be further tested experimentally within the general AD framework. Electronic supplementary material The online version of this article (10.1007/s00401-019-02004-0) contains supplementary material, which is available to authorized users.

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BIN1 recovers tauopathy-induced long-term memory deficits in mice and interacts with Tau through Thr348 phosphorylation

et al. 2019

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The bridging integrator 1 gene (BIN1) is a major genetic risk factor for Alzheimer’s disease (AD). In this report, we investigated how BIN1-dependent pathophysiological processes might be associated with Tau. We first generated a cohort of control and transgenic mice either overexpressing human MAPT (TgMAPT) or both human MAPT and BIN1 (TgMAPT;TgBIN1), which we followed-up from 3 to 15 months. In TgMAPT;TgBIN1 mice short-term memory deficits appeared earlier than in TgMAPT mice; however—unlike TgMAPT mice—TgMAPT;TgBIN1 mice did not exhibit any long-term or spatial memory deficits for at least 15 months. After killing the cohort at 18 months, immunohistochemistry revealed that BIN1 overexpression prevents both Tau mislocalization and somatic inclusion in the hippocampus, where an increase in BIN1–Tau interaction was also observed. We then sought mechanisms controlling the BIN1–Tau interaction. We developed a high-content screening approach to characterize modulators of the BIN1–Tau interaction in an agnostic way (1,126 compounds targeting multiple pathways), and we identified—among others—an inhibitor of calcineurin, a Ser/Thr phosphatase. We determined that calcineurin dephosphorylates BIN1 on a cyclin-dependent kinase phosphorylation site at T348, promoting the open conformation of the neuronal BIN1 isoform. Phosphorylation of this site increases the availability of the BIN1 SH3 domain for Tau interaction, as demonstrated by nuclear magnetic resonance experiments and in primary neurons. Finally, we observed that although the levels of the neuronal BIN1 isoform were unchanged in AD brains, phospho-BIN1(T348):BIN1 ratio was increased, suggesting a compensatory mechanism. In conclusion, our data support the idea that BIN1 modulates the AD risk through an intricate regulation of its interaction with Tau. Alteration in BIN1 expression or activity may disrupt this regulatory balance with Tau and have direct effects on learning and memory.Electronic supplementary materialThe online version of this article (10.1007/s00401-019-02017-9) contains supplementary material, which is available to authorized users.

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Regulation of the interaction between the neuronal BIN1 isoform 1 and Tau proteins – role of the SH3 domain

Cited by 36 publications

References 37 publications

Effect of BIN1 on cardiac dysfunction and malignant arrhythmias

Effect of BIN1 on cardiac dysfunction and malignant arrhythmias

The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis?

BIN1 recovers tauopathy-induced long-term memory deficits in mice and interacts with Tau through Thr348 phosphorylation

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