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Gene Review

Bin1  -  bridging integrator 1

Mus musculus

Synonyms: ALP-1, Amphiphysin 2, Amphiphysin II, Amphiphysin-like protein, Amphl, ...
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Disease relevance of Bin1

  • No striking histological abnormalities were evident in skeletal muscle of Bin1 null embryos, but severe ventricular cardiomyopathy was observed in these embryos [1].
  • Bin1 is often attenuated in breast cancer but its ability to negatively modify oncogenesis or progression in this context has not been gauged directly [2].
  • The frequent losses of Bin1 expression that occur in human breast and prostate cancers may promote tumor progression and limit susceptibility to FTI or other therapeutic agents that exploit the heightened sensitivity of neoplastic cells to apoptosis [3].
  • In prostate, Bin1 staining was frequently absent in cases of primary prostate adenocarcinoma [4].

High impact information on Bin1


Biological context of Bin1

  • We cloned and functionally characterized the murine Bin1 gene as a first step to investigate its physiological roles in differentiation, apoptosis, and tumorigenesis [7].
  • Since the human gene was mapped previously to chromosome 2q14, the location of Bin1 defines a previously unrecognized region of synteny between human chromosome 2 and mouse chromosome 18 [7].
  • Consistent with a role for Bin1 in apoptosis, the promoter included a functional consensus motif for activation by NF-kappaB, an important regulator of cell death [7].
  • However, Bin1 is upregulated in embryonic development by E10.5 in myotomes, the progenitors of skeletal muscle, supporting a role in myogenesis and suggesting that the mouse and human genes may be controlled somewhat differently during development [7].
  • In C2C12 myoblasts antisense Bin1 prevents induction of the cell cycle kinase inhibitor p21WAF1, suggesting that it acts at an early time during the muscle differentiation program [7].

Anatomical context of Bin1


Regulatory relationships of Bin1

  • The Bin1 gene encodes a nucleocytosolic adapter protein that interacts with and suppresses the cell transforming activity of Myc [2].
  • In E1A?transformed MEFs, Bin1 loss reduced the susceptibility to apoptosis triggered by tumor necrosis factor-alpha, an effect that was associated with precocious nuclear trafficking of NF-kappaB [8].

Other interactions of Bin1


Analytical, diagnostic and therapeutic context of Bin1

  • Our findings suggest that Bin1 loss promotes immune escape in cancer by deregulating IDO and that IDO inhibitors may improve responses to cancer chemotherapy [12].
  • Immunofluorescence analysis revealed that amphiphysin 2 might bind reticulo-vesicular structures present throughout the cell body and be associated with SNX4 on these structures [13].
  • Functional studies revealed that either the treatment with ALP-1 plus complement of the antigen-primed splenic T cells from non-lpr-bearing mice or the addition of ALP-1 alone all but completely abolished the development of plaque-forming cells against sheep red blood cells in T-B cell coculture [14].
  • The surface antigen profiles of these proliferating cells were analyzed using two-color flow cytometry analysis with two newly established rat monoclonal antibodies (ALP-1, ALP-2) directed to lpr cells [15].


  1. Targeted disruption of the murine Bin1/Amphiphysin II gene does not disable endocytosis but results in embryonic cardiomyopathy with aberrant myofibril formation. Muller, A.J., Baker, J.F., DuHadaway, J.B., Ge, K., Farmer, G., Donover, P.S., Meade, R., Reid, C., Grzanna, R., Roach, A.H., Shah, N., Soler, A.P., Prendergast, G.C. Mol. Cell. Biol. (2003) [Pubmed]
  2. Bin1 ablation in mammary gland delays tissue remodeling and drives cancer progression. Chang, M.Y., Boulden, J., Sutanto-Ward, E., Duhadaway, J.B., Soler, A.P., Muller, A.J., Prendergast, G.C. Cancer Res. (2007) [Pubmed]
  3. Transformation-selective apoptotic program triggered by farnesyltransferase inhibitors requires Bin1. DuHadaway, J.B., Du, W., Donover, S., Baker, J., Liu, A.X., Sharp, D.M., Muller, A.J., Prendergast, G.C. Oncogene (2003) [Pubmed]
  4. Immunohistochemical analysis of Bin1/Amphiphysin II in human tissues: diverse sites of nuclear expression and losses in prostate cancer. DuHadaway, J.B., Lynch, F.J., Brisbay, S., Bueso-Ramos, C., Troncoso, P., McDonnell, T., Prendergast, G.C. J. Cell. Biochem. (2003) [Pubmed]
  5. Amphiphysin IIm, a novel amphiphysin II isoform, is required for macrophage phagocytosis. Gold, E.S., Morrissette, N.S., Underhill, D.M., Guo, J., Bassetti, M., Aderem, A. Immunity (2000) [Pubmed]
  6. The amphiphysin-like protein 1 (ALP1) interacts functionally with the cABL tyrosine kinase and may play a role in cytoskeletal regulation. Kadlec, L., Pendergast, A.M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  7. The murine Bin1 gene functions early in myogenesis and defines a new region of synteny between mouse chromosome 18 and human chromosome 2. Mao, N.C., Steingrimsson, E., DuHadaway, J., Wasserman, W., Ruiz, J.C., Copeland, N.G., Jenkins, N.A., Prendergast, G.C. Genomics (1999) [Pubmed]
  8. Targeted deletion of the suppressor gene bin1/amphiphysin2 accentuates the neoplastic character of transformed mouse fibroblasts. Muller, A.J., DuHadaway, J.B., Donover, P.S., Sutanto-Ward, E., Prendergast, G.C. Cancer Biol. Ther. (2004) [Pubmed]
  9. Decreased synaptic vesicle recycling efficiency and cognitive deficits in amphiphysin 1 knockout mice. Di Paolo, G., Sankaranarayanan, S., Wenk, M.R., Daniell, L., Perucco, E., Caldarone, B.J., Flavell, R., Picciotto, M.R., Ryan, T.A., Cremona, O., De Camilli, P. Neuron (2002) [Pubmed]
  10. Role of amphiphysin II in somatostatin receptor trafficking in neuroendocrine cells. Sarret, P., Esdaile, M.J., McPherson, P.S., Schonbrunn, A., Kreienkamp, H.J., Beaudet, A. J. Biol. Chem. (2004) [Pubmed]
  11. Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle. Lee, E., Marcucci, M., Daniell, L., Pypaert, M., Weisz, O.A., Ochoa, G.C., Farsad, K., Wenk, M.R., De Camilli, P. Science (2002) [Pubmed]
  12. Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Muller, A.J., DuHadaway, J.B., Donover, P.S., Sutanto-Ward, E., Prendergast, G.C. Nat. Med. (2005) [Pubmed]
  13. Sorting nexin 4 and amphiphysin 2, a new partnership between endocytosis and intracellular trafficking. Leprince, C., Le Scolan, E., Meunier, B., Fraisier, V., Brandon, N., De Gunzburg, J., Camonis, J. J. Cell. Sci. (2003) [Pubmed]
  14. T cells bearing unique membrane antigen and their regulatory role in humoral immune response in mice. Ishida, Y., Sekigawa, I., Hamaoki, M., Takenouchi, T., Yumura, W., Sato, H., Shirai, T. Eur. J. Immunol. (1986) [Pubmed]
  15. Unique cell surface phenotypes of proliferating lymphocytes in mice homozygous for lpr and gld mutations, defined by monoclonal antibodies to MRL/Mp-lpr/lpr T cells. Ishida, Y., Ueda, G., Noguchi, K., Nagasawa, R., Hirose, S., Sato, H., Shirai, T. Cell. Immunol. (1987) [Pubmed]
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