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

• Amphiphysin II participates in receptor-mediated endocytosis, in part, by recruiting the GTPase dynamin to the nascent endosome [5].
• Amphiphysin IIm, a novel amphiphysin II isoform, is required for macrophage phagocytosis [5].
• We demonstrate here that a novel isoform of amphiphysin II associates with early phagosomes in macrophages [5].
• We have ablated the dynamin-binding site of this protein and shown that this mutant form of amphiphysin II inhibits phagocytosis at the stage of membrane extension around the bound particles [5].
• The amphiphysin-like protein 1 (ALP1) interacts functionally with the cABL tyrosine kinase and may play a role in cytoskeletal regulation [6].

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

• Similarly, actin cytoskeletal organization, proliferation, and apoptosis in embryo fibroblasts were all unaffected by Bin1 loss [1].
• Bin1 has been reported to affect muscle cell differentiation and T-tubule formation [1].
• Bin1 loss had no discernible impact on either endocytosis or phagocytosis in mouse embryo-derived fibroblasts and macrophages, respectively [1].
• Ultrastructurally, myofibrils in ventricular cardiomyocytes of Bin1 null embryos were severely disorganized [1].
• These results define a developmentally critical role for the Bin1 gene in cardiac muscle development [1].

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

• We have now generated amphiphysin 1 knockout mice and found that lack of amphiphysin 1 causes a parallel dramatic reduction of amphiphysin 2 selectively in brain [9].
• Role of amphiphysin II in somatostatin receptor trafficking in neuroendocrine cells [10].
• While these properties may reflect the ability of these isoforms to interact with and suppress the cell transforming activity of c-Myc, the effects of Bin1 deletion on the oncogenicity of c-myc or other transforming genes has not been gauged directly [8].
• In developing myotubes, amphiphysin 2 and caveolin-3 segregated in tubular and vesicular portions of the T-tubule system, respectively [11].

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].

References