BIN1 explained

Myc box-dependent-interacting protein 1, also known as Bridging Integrator-1 and Amphiphysin-2 is a protein that in humans is encoded by the BIN1 gene.^{[1] [2] [3]}

This gene encodes several isoforms of a nucleocytoplasmic adaptor protein, one of which was initially identified as a MYC-interacting protein with features of a tumor suppressor.

Isoforms that are expressed in the central nervous system may be involved in synaptic vesicle endocytosis and may interact with dynanim, synaptojanin, endophilin, and clathrin.

Isoforms that are expressed in muscle and ubiquitously expressed isoforms localize to the cytoplasm and nucleus and activate a caspase-independent apoptotic process.

Studies in mouse suggest that this gene plays an important role in cardiac muscle development. Alternate splicing of the gene results in ten transcript variants encoding different isoforms. Aberrant splice variants expressed in tumor cell lines have also been described.^[4]

Clinical significance

In humans, mutations in BIN1 have been associated with skeletal myopathies including centronuclear myopathy causing muscle weakness^[3] and myotonic dystrophy causing progressive muscle wasting, myotonia, cataracts, and heart conduction defects.^[5] An association has also been found between BIN1 mutations and Alzheimer's disease. Knockdown of BIN1 produces a cardiomyopathy phenotype in zebrafish,^[6] and in sheep BIN1 may be responsible for the loss of T-tubules seen in heart failure.^[7]

Interactions

BIN1 has been shown to interact with Phospholipase D1,^[8] SNX4^[9] and PLD2.^[8]

Further reading

• Andersson B, Wentland MA, Ricafrente JY . A "double adaptor" method for improved shotgun library construction. . Anal. Biochem. . 236 . 1 . 107–13 . 1996 . 8619474 . 10.1006/abio.1996.0138 . etal.
• Yu W, Andersson B, Worley KC . Large-Scale Concatenation cDNA Sequencing . Genome Res. . 7 . 4 . 353–8 . 1997 . 9110174 . 10.1101/gr.7.4.353. 139146 . etal.
• Leprince C, Romero F, Cussac D . A new member of the amphiphysin family connecting endocytosis and signal transduction pathways . J. Biol. Chem. . 272 . 24 . 15101–5 . 1997 . 9182529 . 10.1074/jbc.272.24.15101 . etal. free .
• Butler MH, David C, Ochoa GC . Amphiphysin II (SH3P9; BIN1), a Member of the Amphiphysin/Rvs Family, Is Concentrated in the Cortical Cytomatrix of Axon Initial Segments and Nodes of Ranvier in Brain and around T Tubules in Skeletal Muscle . J. Cell Biol. . 137 . 6 . 1355–67 . 1997 . 9182667 . 10.1083/jcb.137.6.1355 . 2132527 . etal.
• Ramjaun AR, Micheva KD, Bouchelet I, McPherson PS . Identification and characterization of a nerve terminal-enriched amphiphysin isoform . J. Biol. Chem. . 272 . 26 . 16700–6 . 1997 . 9195986 . 10.1074/jbc.272.26.16700 . free .
• Tsutsui K, Maeda Y, Tsutsui K . cDNA cloning of a novel amphiphysin isoform and tissue-specific expression of its multiple splice variants . Biochem. Biophys. Res. Commun. . 236 . 1 . 178–83 . 1997 . 9223448 . 10.1006/bbrc.1997.6927 . etal.
• McMahon HT, Wigge P, Smith C . Clathrin interacts specifically with amphiphysin and is displaced by dynamin . FEBS Lett. . 413 . 2 . 319–22 . 1997 . 9280305 . 10.1016/S0014-5793(97)00928-9 . 42520828 . free .
• Micheva KD, Ramjaun AR, Kay BK, McPherson PS . SH3 domain-dependent interactions of endophilin with amphiphysin . FEBS Lett. . 414 . 2 . 308–12 . 1997 . 9315708 . 10.1016/S0014-5793(97)01016-8 . 21328416 . free .
• Micheva KD, Kay BK, McPherson PS . Synaptojanin forms two separate complexes in the nerve terminal. Interactions with endophilin and amphiphysin . J. Biol. Chem. . 272 . 43 . 27239–45 . 1997 . 9341169 . 10.1074/jbc.272.43.27239 . free .
• Wigge P, Köhler K, Vallis Y . Amphiphysin Heterodimers: Potential Role in Clathrin-mediated Endocytosis . Mol. Biol. Cell . 8 . 10 . 2003–15 . 1997 . 9348539 . 10.1091/mbc.8.10.2003. 25662 . etal.
• Kadlec L, Pendergast AM . The amphiphysin-like protein 1 (ALP1) interacts functionally with the cABL tyrosine kinase and may play a role in cytoskeletal regulation . Proc. Natl. Acad. Sci. U.S.A. . 94 . 23 . 12390–5 . 1997 . 9356459 . 10.1073/pnas.94.23.12390 . 24959 . 1997PNAS...9412390K . free .
• Wechsler-Reya R, Sakamuro D, Zhang J . Structural analysis of the human BIN1 gene. Evidence for tissue-specific transcriptional regulation and alternate RNA splicing . J. Biol. Chem. . 272 . 50 . 31453–8 . 1998 . 9395479 . 10.1074/jbc.272.50.31453 . etal. free .
• Wechsler-Reya RJ, Elliott KJ, Prendergast GC . A Role for the Putative Tumor Suppressor Bin1 in Muscle Cell Differentiation . Mol. Cell. Biol. . 18 . 1 . 566–75 . 1998 . 9418903 . 10.1128/MCB.18.1.566. 121524 .
• Ramjaun AR, McPherson PS . Multiple amphiphysin II splice variants display differential clathrin binding: identification of two distinct clathrin-binding sites . J. Neurochem. . 70 . 6 . 2369–76 . 1998 . 9603201 . 10.1046/j.1471-4159.1998.70062369.x . 21910795 . free .
• Mao NC, Steingrimsson E, DuHadaway J . The murine Bin1 gene functions early in myogenesis and defines a new region of synteny between mouse chromosome 18 and human chromosome 2 . Genomics . 56 . 1 . 51–8 . 1999 . 10036185 . 10.1006/geno.1998.5709 . etal.
• Wixler V, Laplantine E, Geerts D . Identification of novel interaction partners for the conserved membrane proximal region of alpha-integrin cytoplasmic domains . FEBS Lett. . 445 . 2–3 . 351–5 . 1999 . 10094488 . 10.1016/S0014-5793(99)00151-9 . 9218762 . etal. free .
• Ramjaun AR, Philie J, de Heuvel E, McPherson PS . The N terminus of amphiphysin II mediates dimerization and plasma membrane targeting . J. Biol. Chem. . 274 . 28 . 19785–91 . 1999 . 10391921 . 10.1074/jbc.274.28.19785 . free .
• Traub LM, Downs MA, Westrich JL, Fremont DH . Crystal structure of the α appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly . Proc. Natl. Acad. Sci. U.S.A. . 96 . 16 . 8907–12 . 1999 . 10430869 . 10.1073/pnas.96.16.8907 . 17706 . 1999PNAS...96.8907T . free .
• Web site: Genetic study of Lewy body dementia supports ties to Alzheimer's and Parkinson's diseases . National Institutes of Health (NIH) . 2021-02-16 . 2023-08-07.

Notes and References

1. Negorev D, Riethman H, Wechsler-Reya R, Sakamuro D, Prendergast GC, Simon D . The Bin1 gene localizes to human chromosome 2q14 by PCR analysis of somatic cell hybrids and fluorescence in situ hybridization . Genomics . 33 . 2 . 329–31 . January 1997 . 8725406 . 10.1006/geno.1996.0205 .
2. Sakamuro D, Elliott KJ, Wechsler-Reya R, Prendergast GC . BIN1 is a novel MYC-interacting protein with features of a tumour suppressor . Nat Genet . 14 . 1 . 69–77 . October 1996 . 8782822 . 10.1038/ng0996-69 . 21484402 .
3. Nicot AS, Toussaint A, Tosch V, Kretz C, Wallgren-Pettersson C, Iwarsson E, Kingston H, Garnier JM, Biancalana V, Oldfors A, Mandel JL, Laporte J . Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy . Nat Genet . 39 . 9 . 1134–9 . August 2007 . 17676042 . 10.1038/ng2086 . 16861439 .
4. Web site: Entrez Gene: BIN1 bridging integrator 1.
5. Prokic. Ivana. Belinda Cowling . Cowling. Belinda S.. Laporte. Jocelyn. May 2014. Amphiphysin 2 (BIN1) in physiology and diseases. Journal of Molecular Medicine. 92. 5. 453–463. 10.1007/s00109-014-1138-1. 1432-1440. 24590001. 14038898.
6. Hong. Ting-Ting. Smyth. James W.. Chu. Kevin Y.. Vogan. Jacob M.. Fong. Tina S.. Jensen. Brian C.. Fang. Kun. Halushka. Marc K.. Russell. Stuart D.. May 2012. BIN1 is reduced and Cav1.2 trafficking is impaired in human failing cardiomyocytes. Heart Rhythm. 9. 5. 812–820. 10.1016/j.hrthm.2011.11.055. 1556-3871. 3306544. 22138472.
7. Caldwell. Jessica L.. Smith. Charlotte E. R.. Taylor. Rebecca F.. Kitmitto. Ashraf. Eisner. David A.. Dibb. Katharine M.. Trafford. Andrew W.. 2014-12-05. Dependence of cardiac transverse tubules on the BAR domain protein amphiphysin II (BIN-1). Circulation Research. 115. 12. 986–996. 10.1161/CIRCRESAHA.116.303448. 1524-4571. 4274343. 25332206.
8. Lee . C . Kim S R. Chung J K. Frohman M A. Kilimann M W. Rhee S G . June 2000 . Inhibition of phospholipase D by amphiphysins . J. Biol. Chem. . 275 . 25 . 18751–8 . 0021-9258. 10764771 . 10.1074/jbc.M001695200 . free .
9. Leprince . Corinne . Le Scolan Erwan . Meunier Brigitte . Fraisier Vincent . Brandon Nathalie . De Gunzburg Jean . Camonis Jacques . May 2003 . Sorting nexin 4 and amphiphysin 2, a new partnership between endocytosis and intracellular trafficking . J. Cell Sci. . 116 . Pt 10 . 1937–48 . 0021-9533. 12668730 . 10.1242/jcs.00403 . free .