NAPA (gene) explained

N-ethylmaleimide-sensitive factor Attachment Protein Alpha, also known as SNAP-α, is a SNAP protein that is involved in the intra-cellular trafficking and fusing of vesicles to target membranes in cells.^[1]

Function

The 'SNARE hypothesis' is a model explaining the process of docking and fusion of vesicles to their target membranes. According to this model, membrane proteins from the vesicle (v-SNAREs) and proteins from the target membrane (t-SNAREs) govern the specificity of vesicle targeting and docking through mutual recognition. Once the 2 classes of SNAREs bind to each other, they form a complex that recruits the general elements of the fusion apparatus, namely NSF (N-ethylmaleimide-sensitive factor) and SNAPs (soluble NSF-attachment proteins), to the site of membrane fusion, thereby forming the 20S fusion complex. Alpha- and gamma-SNAP are found in a wide range of tissues and act synergistically in intra-Golgi transport. The sequence of the predicted 295-amino acid human protein encoded by NAPA shares 37%, 60%, and 67% identity with the sequences of yeast, Drosophila, and squid alpha-SNAP, respectively. Platelets contain some of the same proteins, including NSF, p115/TAP, alpha-SNAP (this protein), gamma-SNAP, and the t-SNAREs syntaxin-2 and syntaxin-4, that are used in many vesicular transport processes in other cell types. Platelet exocytosis uses a molecular mechanism similar to that used by other secretory cells, such as neurons, although the proteins used by the platelet and their modes of regulation may be quite different.

Clinical significance

NAPA is abnormally expressed in fetuses of both IVF and ICSI, which may contribute to the increased risk of birth defects in these methods of assisted reproductive technology (ART).^[2]

Interactions

NAPA has been shown to interact with:

• NSF,^[3]
• SNAP23,
• STX1A,^{[4] [5]}
• STX4,^[6]
• STX5.^{[6] [7]}
• ORAI1, STIM1.^[8]

Further reading

• Wilson DW, Whiteheart SW, Wiedmann M, Brunner M, Rothman JE . A multisubunit particle implicated in membrane fusion . J. Cell Biol. . 117 . 3 . 531–8 . 1992 . 1315316 . 2289450 . 10.1083/jcb.117.3.531 .
• Whiteheart SW, Brunner M, Wilson DW, Wiedmann M, Rothman JE . Soluble N-ethylmaleimide-sensitive fusion attachment proteins (SNAPs) bind to a multi-SNAP receptor complex in Golgi membranes . J. Biol. Chem. . 267 . 17 . 12239–43 . 1992 . 10.1016/S0021-9258(19)49830-X . 1601890 . free .
• Hanson PI, Otto H, Barton N, Jahn R . The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin . J. Biol. Chem. . 270 . 28 . 16955–61 . 1995 . 7622514 . 10.1074/jbc.270.28.16955 . free .
• Whiteheart SW, Griff IC, Brunner M, Clary DO, Mayer T, Buhrow SA, Rothman JE . SNAP family of NSF attachment proteins includes a brain-specific isoform . Nature . 362 . 6418 . 353–5 . 1993 . 8455721 . 10.1038/362353a0 . 1993Natur.362..353W . 4341471 .
• Timmers KI, Clark AE, Omatsu-Kanbe M, Whiteheart SW, Bennett MK, Holman GD, Cushman SW . Identification of SNAP receptors in rat adipose cell membrane fractions and in SNARE complexes co-immunoprecipitated with epitope-tagged N-ethylmaleimide-sensitive fusion protein . Biochem. J. . 320 . Pt 2 . 429–36 . 1997 . 8973549 . 1217948 . 10.1042/bj3200429.
• Lemons PP, Chen D, Bernstein AM, Bennett MK, Whiteheart SW . Regulated secretion in platelets: identification of elements of the platelet exocytosis machinery . Blood . 90 . 4 . 1490–500 . 1997 . 9269766 . 10.1182/blood.V90.4.1490. free .
• Subramaniam VN, Loh E, Hong W . N-Ethylmaleimide-sensitive factor (NSF) and alpha-soluble NSF attachment proteins (SNAP) mediate dissociation of GS28-syntaxin 5 Golgi SNAP receptors (SNARE) complex . J. Biol. Chem. . 272 . 41 . 25441–4 . 1997 . 9325254 . 10.1074/jbc.272.41.25441 . free .
• Lowe SL, Peter F, Subramaniam VN, Wong SH, Hong W . A SNARE involved in protein transport through the Golgi apparatus . Nature . 389 . 6653 . 881–4 . 1997 . 9349823 . 10.1038/39923 . 1997Natur.389..881L . 4421051 .
• Barnard RJ, Morgan A, Burgoyne RD . Stimulation of NSF ATPase Activity by α-SNAP Is Required for SNARE Complex Disassembly and Exocytosis . J. Cell Biol. . 139 . 4 . 875–83 . 1997 . 9362506 . 2139964 . 10.1083/jcb.139.4.875 .
• Wong SH, Xu Y, Zhang T, Hong W . Syntaxin 7, a novel syntaxin member associated with the early endosomal compartment . J. Biol. Chem. . 273 . 1 . 375–80 . 1998 . 9417091 . 10.1074/jbc.273.1.375 . free .
• Tang BL, Tan AE, Lim LK, Lee SS, Low DY, Hong W . Syntaxin 12, a member of the syntaxin family localized to the endosome . J. Biol. Chem. . 273 . 12 . 6944–50 . 1998 . 9507000 . 10.1074/jbc.273.12.6944 . free .
• Wong SH, Zhang T, Xu Y, Subramaniam VN, Griffiths G, Hong W . Endobrevin, a Novel Synaptobrevin/VAMP-Like Protein Preferentially Associated with the Early Endosome . Mol. Biol. Cell . 9 . 6 . 1549–63 . 1998 . 9614193 . 25382 . 10.1091/mbc.9.6.1549 .
• Osten P, Srivastava S, Inman GJ, Vilim FS, Khatri L, Lee LM, States BA, Einheber S, Milner TA, Hanson PI, Ziff EB . The AMPA receptor GluR2 C terminus can mediate a reversible, ATP-dependent interaction with NSF and alpha- and beta-SNAPs . Neuron . 21 . 1 . 99–110 . 1998 . 9697855 . 10.1016/S0896-6273(00)80518-8 . 18569829 . free .
• Prekeris R, Klumperman J, Chen YA, Scheller RH . Syntaxin 13 Mediates Cycling of Plasma Membrane Proteins via Tubulovesicular Recycling Endosomes . J. Cell Biol. . 143 . 4 . 957–71 . 1998 . 9817754 . 2132958 . 10.1083/jcb.143.4.957 .
• Nagamatsu S, Watanabe T, Nakamichi Y, Yamamura C, Tsuzuki K, Matsushima S . alpha-soluble N-ethylmaleimide-sensitive factor attachment protein is expressed in pancreatic beta cells and functions in insulin but not gamma-aminobutyric acid secretion . J. Biol. Chem. . 274 . 12 . 8053–60 . 1999 . 10075705 . 10.1074/jbc.274.12.8053 . free .
• Subramaniam VN, Loh E, Horstmann H, Habermann A, Xu Y, Coe J, Griffiths G, Hong W . Preferential association of syntaxin 8 with the early endosome . J. Cell Sci. . 113 . 6 . 997–1008 . 2000 . 10.1242/jcs.113.6.997 . 10683148 .
• Hirose H, Arasaki K, Dohmae N, Takio K, Hatsuzawa K, Nagahama M, Tani K, Yamamoto A, Tohyama M, Tagaya M . Implication of ZW10 in membrane trafficking between the endoplasmic reticulum and Golgi . EMBO J. . 23 . 6 . 1267–78 . 2005 . 15029241 . 381410 . 10.1038/sj.emboj.7600135 .
• Singh BB, Lockwich TP, Bandyopadhyay BC, Liu X, Bollimuntha S, Brazer SC, Combs C, Das S, Leenders AG, Sheng ZH, Knepper MA, Ambudkar SV, Ambudkar IS . VAMP2-dependent exocytosis regulates plasma membrane insertion of TRPC3 channels and contributes to agonist-stimulated Ca2+ influx . Mol. Cell . 15 . 4 . 635–46 . 2004 . 15327778 . 10.1016/j.molcel.2004.07.010 . free .

Notes and References

1. 2111733 . 61 . 4 . SNAPs, a family of NSF attachment proteins involved in intracellular membrane fusion in animals and yeast . 1990 . Cell . 709–21 . 10.1016/0092-8674(90)90482-t . Clary DO, Griff IC, Rothman JE. 11468679 . free .
2. Zhang Y, Zhang YL, Feng C, Wu YT, Liu AX, Sheng JZ, Cai J, Huang HF . Comparative proteomic analysis of human placenta derived from assisted reproductive technology . Proteomics . 8 . 20 . 4344–56 . September 2008 . 18792929 . 10.1002/pmic.200800294 . 206362532 .
3. Barnard RJ, Morgan A, Burgoyne RD . Stimulation of NSF ATPase activity by alpha-SNAP is required for SNARE complex disassembly and exocytosis . J. Cell Biol. . 139 . 4 . 875–83 . Nov 1997 . 9362506 . 2139964 . 10.1083/jcb.139.4.875.
4. Hanson PI, Otto H, Barton N, Jahn R . The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin . J. Biol. Chem. . 270 . 28 . 16955–61 . Jul 1995 . 7622514 . 10.1074/jbc.270.28.16955. free .
5. McMahon HT, Missler M, Li C, Südhof TC . Complexins: cytosolic proteins that regulate SNAP receptor function . Cell . 83 . 1 . 111–9 . Oct 1995 . 7553862 . 10.1016/0092-8674(95)90239-2. 675343 . free .
6. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
7. Rabouille C, Kondo H, Newman R, Hui N, Freemont P, Warren G . Syntaxin 5 is a common component of the NSF- and p97-mediated reassembly pathways of Golgi cisternae from mitotic Golgi fragments in vitro . Cell . 92 . 5 . 603–10 . Mar 1998 . 9506515 . 10.1016/s0092-8674(00)81128-9. 17285800 . free .
8. Miao Y, Miner C, Zhang L, Hanson PI, Dani A, Vig M . An essential and NSF independent role for α-SNAP in store-operated calcium entry . eLife . July 2013 . 23878724 . 10.7554/eLife.00802 . 2 . 3713520 . e00802 . free .