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

Further reading

External links

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 .