Amphiphysin Explained

Amphiphysin is a protein that in humans is encoded by the AMPH gene.^{[1] [2]}

Function

This gene encodes a protein associated with the cytoplasmic surface of synaptic vesicles. A subset of patients with stiff person syndrome who were also affected by breast cancer are positive for autoantibodies against this protein. Alternate splicing of this gene results in two transcript variants encoding different isoforms. Additional splice variants have been described, but their full length sequences have not been determined.

Amphiphysin is a brain-enriched protein with an N-terminal lipid interaction, dimerisation and membrane bending BAR domain, a middle clathrin and adaptor binding domain and a C-terminal SH3 domain. In the brain, its primary function is thought to be the recruitment of dynamin to sites of clathrin-mediated endocytosis. There are 2 mammalian amphiphysins with similar overall structure. A ubiquitous splice form of amphiphysin-2 (BIN1) that does not contain clathrin or adaptor interactions is highly expressed in muscle tissue and is involved in the formation and stabilization of the T-tubule network. In other tissues amphiphysin is likely involved in other membrane bending and curvature stabilization events.

Interactions

Amphiphysin has been shown to interact with DNM1,^{[3] [4] [5] [6] [7]} Phospholipase D1,^[8] CDK5R1,^[9] PLD2,^[8] CABIN1^[10] and SH3GL2.^{[3] [11]}

See also

• AP180
• Epsin

Further reading

• Lichte B, Veh RW, Meyer HE, Kilimann MW . Amphiphysin, a novel protein associated with synaptic vesicles . The EMBO Journal . 11 . 7 . 2521–30 . July 1992 . 1628617 . 556727 . 10.1002/j.1460-2075.1992.tb05317.x .
• Yamamoto R, Li X, Winter S, Francke U, Kilimann MW . Primary structure of human amphiphysin, the dominant autoantigen of paraneoplastic stiff-man syndrome, and mapping of its gene (AMPH) to chromosome 7p13-p14 . Human Molecular Genetics . 4 . 2 . 265–8 . February 1995 . 7757077 . 10.1093/hmg/4.2.265 .
• David C, Solimena M, De Camilli P . Autoimmunity in stiff-Man syndrome with breast cancer is targeted to the C-terminal region of human amphiphysin, a protein similar to the yeast proteins, Rvs167 and Rvs161 . FEBS Letters . 351 . 1 . 73–9 . August 1994 . 8076697 . 10.1016/0014-5793(94)00826-4 . 133561 . free .
• David C, McPherson PS, Mundigl O, de Camilli P . A role of amphiphysin in synaptic vesicle endocytosis suggested by its binding to dynamin in nerve terminals . Proceedings of the National Academy of Sciences of the United States of America . 93 . 1 . 331–5 . January 1996 . 8552632 . 40232 . 10.1073/pnas.93.1.331 . 1996PNAS...93..331D . free .
• Grabs D, Slepnev VI, Songyang Z, David C, Lynch M, Cantley LC, De Camilli P . The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence . The Journal of Biological Chemistry . 272 . 20 . 13419–25 . May 1997 . 9148966 . 10.1074/jbc.272.20.13419 . free .
• Butler MH, David C, Ochoa GC, Freyberg Z, Daniell L, Grabs D, Cremona O, De Camilli P . 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 . The Journal of Cell Biology . 137 . 6 . 1355–67 . June 1997 . 9182667 . 2132527 . 10.1083/jcb.137.6.1355 .
• Ramjaun AR, Micheva KD, Bouchelet I, McPherson PS . Identification and characterization of a nerve terminal-enriched amphiphysin isoform . The Journal of Biological Chemistry . 272 . 26 . 16700–6 . June 1997 . 9195986 . 10.1074/jbc.272.26.16700 . free .
• McMahon HT, Wigge P, Smith C . Clathrin interacts specifically with amphiphysin and is displaced by dynamin . FEBS Letters . 413 . 2 . 319–22 . August 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 Letters . 414 . 2 . 308–12 . September 1997 . 9315708 . 10.1016/S0014-5793(97)01016-8 . 21328416 . free .
• Wigge P, Köhler K, Vallis Y, Doyle CA, Owen D, Hunt SP, McMahon HT . Amphiphysin heterodimers: potential role in clathrin-mediated endocytosis . Molecular Biology of the Cell . 8 . 10 . 2003–15 . October 1997 . 9348539 . 25662 . 10.1091/mbc.8.10.2003 .
• Floyd S, Butler MH, Cremona O, David C, Freyberg Z, Zhang X, Solimena M, Tokunaga A, Ishizu H, Tsutsui K, De Camilli P . Expression of amphiphysin I, an autoantigen of paraneoplastic neurological syndromes, in breast cancer . Molecular Medicine . 4 . 1 . 29–39 . January 1998 . 9513187 . 2230265 . 8 . 10.1007/BF03401727 .
• Ramjaun AR, McPherson PS . Multiple amphiphysin II splice variants display differential clathrin binding: identification of two distinct clathrin-binding sites . Journal of Neurochemistry . 70 . 6 . 2369–76 . June 1998 . 9603201 . 10.1046/j.1471-4159.1998.70062369.x . 21910795 . free .
• Slepnev VI, Ochoa GC, Butler MH, Grabs D, De Camilli P . Role of phosphorylation in regulation of the assembly of endocytic coat complexes . Science . 281 . 5378 . 821–4 . August 1998 . 9694653 . 10.1126/science.281.5378.821 . 1998Sci...281..821S .
• Cestra G, Castagnoli L, Dente L, Minenkova O, Petrelli A, Migone N, Hoffmüller U, Schneider-Mergener J, Cesareni G . The SH3 domains of endophilin and amphiphysin bind to the proline-rich region of synaptojanin 1 at distinct sites that display an unconventional binding specificity . The Journal of Biological Chemistry . 274 . 45 . 32001–7 . November 1999 . 10542231 . 10.1074/jbc.274.45.32001 . free .
• Slepnev VI, Ochoa GC, Butler MH, De Camilli P . Tandem arrangement of the clathrin and AP-2 binding domains in amphiphysin 1 and disruption of clathrin coat function by amphiphysin fragments comprising these sites . The Journal of Biological Chemistry . 275 . 23 . 17583–9 . June 2000 . 10748223 . 10.1074/jbc.M910430199 . free .
• Lee C, Kim SR, Chung JK, Frohman MA, Kilimann MW, Rhee SG . Inhibition of phospholipase D by amphiphysins . The Journal of Biological Chemistry . 275 . 25 . 18751–8 . June 2000 . 10764771 . 10.1074/jbc.M001695200 . free .
• Onofri F, Giovedi S, Kao HT, Valtorta F, Bongiorno Borbone L, De Camilli P, Greengard P, Benfenati F . Specificity of the binding of synapsin I to Src homology 3 domains . The Journal of Biological Chemistry . 275 . 38 . 29857–67 . September 2000 . 10899172 . 10.1074/jbc.M006018200 . free .
• Lai MM, Luo HR, Burnett PE, Hong JJ, Snyder SH . The calcineurin-binding protein cain is a negative regulator of synaptic vesicle endocytosis . The Journal of Biological Chemistry . 275 . 44 . 34017–20 . November 2000 . 10931822 . 10.1074/jbc.C000429200 . free .
• Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P . Amphiphysin 1 binds the cyclin-dependent kinase (cdk) 5 regulatory subunit p35 and is phosphorylated by cdk5 and cdc2 . The Journal of Biological Chemistry . 276 . 11 . 8104–10 . March 2001 . 11113134 . 10.1074/jbc.M008932200 . free .
• Leventis PA, Chow BM, Stewart BA, Iyengar B, Campos AR, Boulianne GL . Drosophila Amphiphysin is a post-synaptic protein required for normal locomotion but not endocytosis . Traffic . 2 . 11 . 839–50 . November 2001 . 11733051 . 10.1034/j.1600-0854.2001.21113.x . 42486176 . free .
• Zhang B, Zelhof AC . Amphiphysins: raising the BAR for synaptic vesicle recycling and membrane dynamics. Bin-Amphiphysin-Rvsp . Traffic . 3 . 7 . 452–60 . July 2002 . 12047553 . 10.1034/j.1600-0854.2002.30702.x . 37496168 . Review.
• Zelhof AC, Bao H, Hardy RW, Razzaq A, Zhang B, Doe CQ . Drosophila Amphiphysin is implicated in protein localization and membrane morphogenesis but not in synaptic vesicle endocytosis . Development . 128 . 24 . 5005–15 . December 2001 . 10.1242/dev.128.24.5005 . 11748137 .
• Mathew D, Popescu A, Budnik V . Drosophila amphiphysin functions during synaptic Fasciclin II membrane cycling . The Journal of Neuroscience . 23 . 33 . 10710–6 . November 2003 . 14627656 . 10.1523/JNEUROSCI.23-33-10710.2003 . 6740931 . free .
• Takei K, Slepnev VI, Haucke V, De Camilli P . Functional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis . Nature Cell Biology . 1 . 1 . 33–9 . May 1999 . 10559861 . 10.1038/9004 . 6384633 .
• Peter BJ, Kent HM, Mills IG, Vallis Y, Butler PJ, Evans PR, McMahon HT . BAR domains as sensors of membrane curvature: the amphiphysin BAR structure . Science . 303 . 5657 . 495–9 . January 2004 . 14645856 . 10.1126/science.1092586 . 2004Sci...303..495P . 6104655 . free .
• Evergren E, Marcucci M, Tomilin N, Löw P, Slepnev V, Andersson F, Gad H, Brodin L, De Camilli P, Shupliakov O . Amphiphysin is a component of clathrin coats formed during synaptic vesicle recycling at the lamprey giant synapse . Traffic . 5 . 7 . 514–28 . July 2004 . 15180828 . 10.1111/j.1398-9219.2004.00198.x . 33206924 . 8 . free .
• Razzaq A, Robinson IM, McMahon HT, Skepper JN, Su Y, Zelhof AC, Jackson AP, Gay NJ, O'Kane CJ . Amphiphysin is necessary for organization of the excitation-contraction coupling machinery of muscles, but not for synaptic vesicle endocytosis in Drosophila . Genes & Development . 15 . 22 . 2967–79 . November 2001 . 11711432 . 312829 . 10.1101/gad.207801 .

External links

• Bringing your curves to the bar, amphiphysin home page

Notes and References

1. De Camilli P, Thomas A, Cofiell R, Folli F, Lichte B, Piccolo G, Meinck HM, Austoni M, Fassetta G, Bottazzo G, Bates D, Cartlidge N, Solimena M, Kilimann MW . The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer . The Journal of Experimental Medicine . 178 . 6 . 2219–23 . December 1993 . 8245793 . 2191289 . 10.1084/jem.178.6.2219 . 8 .
2. Web site: Entrez Gene: AMPH amphiphysin (Stiff-Man syndrome with breast cancer 128kDa autoantigen).
3. Micheva KD, Kay BK, McPherson PS . Synaptojanin forms two separate complexes in the nerve terminal. Interactions with endophilin and amphiphysin . The Journal of Biological Chemistry . 272 . 43 . 27239–45 . October 1997 . 9341169 . 10.1074/jbc.272.43.27239 . free .
4. Wigge P, Köhler K, Vallis Y, Doyle CA, Owen D, Hunt SP, McMahon HT . Amphiphysin heterodimers: potential role in clathrin-mediated endocytosis . Molecular Biology of the Cell . 8 . 10 . 2003–15 . October 1997 . 9348539 . 25662 . 10.1091/mbc.8.10.2003 .
5. McMahon HT, Wigge P, Smith C . Clathrin interacts specifically with amphiphysin and is displaced by dynamin . FEBS Letters . 413 . 2 . 319–22 . August 1997 . 9280305 . 10.1016/S0014-5793(97)00928-9 . 42520828 . free .
6. Chen-Hwang MC, Chen HR, Elzinga M, Hwang YW . Dynamin is a minibrain kinase/dual specificity Yak1-related kinase 1A substrate . The Journal of Biological Chemistry . 277 . 20 . 17597–604 . May 2002 . 11877424 . 10.1074/jbc.M111101200 . free .
7. Grabs D, Slepnev VI, Songyang Z, David C, Lynch M, Cantley LC, De Camilli P . The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence . The Journal of Biological Chemistry . 272 . 20 . 13419–25 . May 1997 . 9148966 . 10.1074/jbc.272.20.13419 . free .
8. Lee C, Kim SR, Chung JK, Frohman MA, Kilimann MW, Rhee SG . Inhibition of phospholipase D by amphiphysins . The Journal of Biological Chemistry . 275 . 25 . 18751–8 . June 2000 . 10764771 . 10.1074/jbc.M001695200 . free .
9. Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P . Amphiphysin 1 binds the cyclin-dependent kinase (cdk) 5 regulatory subunit p35 and is phosphorylated by cdk5 and cdc2 . The Journal of Biological Chemistry . 276 . 11 . 8104–10 . March 2001 . 11113134 . 10.1074/jbc.M008932200 . free .
10. Lai MM, Luo HR, Burnett PE, Hong JJ, Snyder SH . The calcineurin-binding protein cain is a negative regulator of synaptic vesicle endocytosis . The Journal of Biological Chemistry . 275 . 44 . 34017–20 . November 2000 . 10931822 . 10.1074/jbc.C000429200 . free .
11. Modregger J, Schmidt AA, Ritter B, Huttner WB, Plomann M . Characterization of Endophilin B1b, a brain-specific membrane-associated lysophosphatidic acid acyl transferase with properties distinct from endophilin A1 . The Journal of Biological Chemistry . 278 . 6 . 4160–7 . February 2003 . 12456676 . 10.1074/jbc.M208568200 . free .