Amphiphysin 2 (BIN1) in physiology and diseases
Abstract
Amphiphysin 2, also named bridging integrator-1 (BIN1) or SH3P9, has been recently implicated in rare and common diseases affecting different tissues and physiological functions. BIN1 downregulation is linked to cancer progression and also correlates with ventricular cardiomyopathy and arrhythmia preceding heart failure. Increased BIN1 expression is linked to increased susceptibility for late-onset Alzheimer's disease. In addition, altered splicing may account for the muscle component of myotonic dystrophies, while recessive germinal mutations cause centronuclear myopathy. Despite undoubtedly underlining the relevance of BIN1 in human diseases, the molecular and cellular bases leading to such different diseases are unclear at present. BIN1 is a key regulator of endocytosis and membrane recycling, cytoskeleton regulation, DNA repair, cell cycle progression, and apoptosis. In light of the recent findings on the molecular, cellular, and physiological roles of BIN1, we discuss potential pathological mechanisms and highlight common disease pathways and also tissue-specific regulation. Next challenges will be to validate BIN1 both as a prognostic marker for the related diseases and as a potential therapeutic target.
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The CLAP domain, encoded by alternatively spliced exons present only in neuronal BIN1 isoforms, is important for BIN1's function in clathrin-mediated endocytosis and synaptic vesicle recycling.
“The CLathrin-Associated Protein binding region (CLAP domain), encoded by alternatively spliced exons present only in the neuronal BIN1 isoforms, is important for BIN1’s function in clathrin-mediated endocytosis and synaptic vesicle recycling [1, 9].”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [1]
A C-terminal SH3 domain found in all BIN1 isoforms mediates interaction with proteins involved in endocytosis such as dynamin, synaptojanin, and endophilin.
“A C-terminal SH3 domain, also found in all isoforms, mediates BIN1 interaction with proteins involved in endocytosis, such as dynamin, synaptojanin, and endophilin [1, 4–6, 14].”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [1]
The BAR domain was initially implicated in lipid binding of BIN1 and in sensing membrane curvature.
“The BAR domain was initially implicated in the lipid binding of BIN1 and in sensing membrane curvature (11,36).”
From BIN1 regulates BACE1 intracellular trafficking and amyloid-β production (2016) · cites this paper as [11]
BIN1, CD2AP and PICALM modulate APP metabolism and the subsequent increase in Aβ production.
“Based on pathway enrichment analyses, three GWAS-defined genes linked with endocytosis (BIN1, CD2AP and PICALM) have been proposed to modulate APP metabolism and the subsequent increase in Aβ production:”
From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [99]
Cites
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“brillary tangles in the brain [94].”
SH3 domain‐dependent interactions of endophilin with amphiphysin
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Loss of Bin1 Promotes the Propagation of Tau Pathology
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“Background The Bridging INtegrator-1 (BIN1; also referred to as amphiphysin II and SH3P9) is a member of the Bin/ Amphiphysin/Rvs (BAR) family of adaptor proteins that regulates membrane dynamics in a variety of cellular functions [1].”
The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory
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“Accordingly, BIN1 recruits some partners (such as AP-2 and clathrin) through its CLAP domain and others (such as dynamin and synaptojanin) through its SH3 domain [14].”
InfluentialSelf-citationBIN1 regulates BACE1 intracellular trafficking and amyloid-β production
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Structural Basis of Tau Interaction With BIN1 and Regulation by Tau Phosphorylation
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- Authors
- Prokic, I., Cowling, B. S., & Laporte, J.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Laporte, Jocelyn
- Venue
- Journal of Molecular Medicine
- Published
- 2014-03-05
- Volume
- 92
- Issue
- 5
- Pages
- 453-463
- ISSN
- 0946-2716 (ISSN-L)
- 1432-1440
- OpenAlex
- W2095715640
- Cited by
- 188
- References
- 7
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 20 · 2023: 13 · 2022: 34 · 2021: 14 · 2020: 13 · 2019: 17 · 2018: 11 · 2017: 10 · 2016: 9 · 2015: 13 · 2014: 6
- FWCI
- 6.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- BIN1, endocytosis, membrane recycling, cardiomyopathy, cardiac arrhythmias, heart failure, Alzheimer's disease, myotonic dystrophy, centronuclear myopathy, splicing, tumor progression, cytoskeleton regulation, DNA repair, apoptosis, prognostic factors, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Cell Cycle, DNA Repair, Gene Expression Regulation, Heart Diseases, Humans, Myotonic Dystrophy, Neoplasms, Nerve Tissue Proteins, Apoptosis, Myopathies, Structural, Congenital
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