Alternative titles; symbols
HGNC Approved Gene Symbol: VAMP7
Cytogenetic location: Xq28 Genomic coordinates (GRCh38): X:155,881,345-155,943,769 (from NCBI)
Exocytosis of vesicle contents requires fusion of opposing membrane layers, and the highly conserved proteins of the SNARE family are crucially involved in this process. SNAREs localized to the vesicle membrane, or v-SNAREs, include VAMP7, and SNAREs localized to the target membrane, or t-SNARES, include the SNAPs (see SNAP25; 600322) and the syntaxins (see STX1A; 186590). The SNARE proteins assemble into a core complex of bundled helices and thereby contribute to membrane fusion (summary by Sander et al., 2008).
From a search for expressed genes in the Xq28 pseudoautosomal region (PAR), D'Esposito et al. (1996) identified a 2,576-bp cDNA encoding a synaptobrevin-like gene. The gene, designated SYBL1, encodes a 220-amino acid polypeptide of 25 kD with 60% similarity (37.5% homology) to an unpublished Arabidopsis gene sequence. SYBL1 was found, unlike all Xp pseudoautosomal genes studied to that time, to undergo X inactivation. In addition, it is also inactive on the Y chromosome, thereby maintaining dosage compensation in an unprecedented way.
Using Northern blot analysis, Matarazzo et al. (1999) found that, like human SYBL1, mouse Sybl1 was ubiquitously expressed.
By immunoblot and immunohistochemical analyses using antibodies against the cytoplasmic domain of VAMP7, Advani et al. (1999) detected expression of a 25-kD membrane-associated protein in multiple mammalian tissues and cell lines. VAMP7 colocalized with LAMP1 (153330), a marker of late endosomes and lysosomes. Immunoelectron microscopy revealed greatest concentration of VAMP7 in the trans-Golgi network. Advani et al. (1999) concluded that the data were consistent with a role for VAMP7 in vesicular transport of proteins from the early endosome to the lysosome.
Matarazzo et al. (1999) determined that the human and mouse VAMP7 genes contain 8 exons.
D'Esposito et al. (1996) identified the SYBL1 gene within the second pseudoautosomal region (PAR2) on chromosome Xq28. The synaptobrevin genes SYB1 (185880) and SYB2 (185881) are autosomal, being located on chromosomes 12 and 17, respectively.
In studies of the pseudoautosomal regions of the X and Y chromosomes, Ciccodicola et al. (2000) sequenced the telomeric 400 kb of the long arm of the human X chromosome, including 330 kb of the human Xq/Yq pseudoautosomal region and the telomere. Sequencing revealed subregions with distinctive regulatory and evolutionary features. The proximal 295 kb contains 2 genes inactivated on both the inactive X and Y chromosomes: SYBL1 and a human homolog of 'sprouty' in Drosophila (SPRY3; 300531). The GC-rich distal 35 kb, added in stages and much later in evolution, contains the X/Y expressed gene IL9R (300007) and the gene CXYorf1 only 5 kb from the Xq telomere. These properties make Xq/YqPAR a model for studies of region-specific gene inactivation, telomere evolution, and involvement in sex-limited conditions.
By investigating promoter DNA methylation profiles, Matarazzo et al. (2002) determined that chromatin on the repressed Xi and the Y alleles of SYBL1 has underacetylated histones H3 and H4 and H3-lysine 9 methylation. The SYBL1 alleles on the inactive X and Y chromosomes were also found to have a condensed chromatin conformation. In contrast, the expressed allele showed H3 and H4 acetylation, H3-lysine-4 methylation, and a less compacted chromatin conformation. In ICF syndrome (242860), a human disease affecting DNA methylation, SYBL1 escapes from silencing, and this correlated with altered patterns of histone methylation and acetylation. The authors suggested that specific combinations of histone methylation and acetylation are involved in the somatic maintenance of permissive and repressed chromatin states at SYBL1. They further suggested that the epigenetic features of the 'Y inactivation' of SYBL1 may be mechanistically similar to those associated with X-chromosome inactivation.
Dietary triacylglycerol is transported from the endoplasmic reticulum (ER) to the cis-Golgi in a specialized vesicle, the prechylomicron transport vesicle (PCTV). Using immunoblot and microscopic analyses, Siddiqi et al. (2006) detected a higher concentration of rat Vamp7 on PCTVs than on ER membranes and showed that Sar1 (see 607690) and Bet1 (605456) colocalized with Vamp7 on PCTVs. Antibodies to Vamp7 reduced the transfer of triacylglycerol, but not protein, from the ER to the Golgi by 85%. Siddiqi et al. (2006) concluded that VAMP7 is enriched in intestinal ER and that it plays a role in the delivery of triacylglycerol from the ER to the Golgi.
Using immunofluorescence and immunoelectron microscopy, Galli et al. (1998) demonstrated that human TIVAMP, syntaxin-3 (STX3A; 600876), and SNAP23 (602534), were insensitive to proteolysis by numerous clostridial neurotoxins (NTs). TIVAMP-containing vesicles were concentrated in the apical domain of epithelial cells. STX3A and SNAP23 were codistributed at the apical plasma membrane, where they formed N-ethyl maleimide-dependent SNARE complexes with TIVAMP and cellubrevin (VAMP3; 603657). Galli et al. (1998) proposed that TIVAMP, STX3A, and SNAP23 participate in exocytotic processes at the apical plasma membrane of epithelial cells and in clostridial NT-resistant pathways.
By immunofluorescence microscopy, Western and Northern blot analyses, and RT-PCR, Mashima et al. (2008) demonstrated that human VAMP7 was present in vacuoles induced by Helicobacter pylori VacA cytotoxin and that it bound syntaxin-7 (STX7; 603217). VacA intoxication increased VAMP7 mRNA expression. Downregulation of VAMP7 by small interfering RNA inhibited VacA-induced vacuolation. Mashima et al. (2008) concluded that VAMP7 plays an important role in VacA-induced vacuolation as the partner of STX7.
Using RT-PCR, immunoblot analysis, and immunofluorescence microscopy, Sander et al. (2008) demonstrated that human intestinal mast cells (MCs) expressed SNAP23, STX1B (601485), STX2 (132350), STX3, STX4 (STX4A; 186591), and STX6 (603944), but not SNAP25. MCs also expressed VAMP3, VAMP7, and VAMP8 (603177), but, in contrast with rodent MCs, they expressed only low levels of VAMP2 (185881). VAMP7 and VAMP8 translocated to the plasma membrane and interacted with SNAP23 and STX4 upon activation. Inhibition of STX4, SNAP23, VAMP7, or VAMP8, but not VAMP2 or VAMP3, resulted in markedly reduced high-affinity IgE receptor-mediated histamine release. Sander et al. (2008) concluded that human MCs express a specific pattern of SNAREs and that VAMP7 and VAMP8, but not VAMP2, are required for rapid degranulation.
Flowerdew and Burgoyne (2009) showed that potassium channel-interacting protein-1 (KCHIP1, or KCNIP1; 604660) interacted with the channel-forming Kv4.2 potassium channel subunit (KCND2; 605410) and was required for Kv4.2 trafficking to the plasma membrane. Using HeLa and mouse Neuro2A neuroblastoma cells, they found that KCHIP1 and Kv4.2 used an intracellular vesicle trafficking pathway that included VTI1A (614316) and VAMP7 and required the GTPase RAB1 (179508), which is shared with more conventional vesicle-trafficking pathways. Knockdown of VTI1A or VAMP7 inhibited transport of Kv4.2 and KCHIP1 to the plasma membrane.
The absence of father-to-son transmission has been observed in a subset of families with bipolar disorder (MAFD2; 309200), suggestive of a susceptibility gene on the sex-linked portion of the X chromosome. This was supported by linkage studies, suggesting the existence of a susceptibility locus near Xq28. Saito et al. (2000) screened the SYBL1 gene for biologically significant mutations that could be tested as candidate alleles in bipolar disorder. They found 4 single nucleotide polymorphisms (SNPs), one of which occurs in a splice site regulatory region (a G-to-C transversion in the ninth nucleotide of the polypyrimidine tract (PPT) located at the 3-prime splice acceptor site at the intron 7/exon8 junction). They analyzed this polymorphism in a population of patients with bipolar disorder and controls and detected a statistical trend toward an association in males with bipolar disorder.
Muller et al. (2002) found modest evidence for an increased frequency of genotypes homozygous for the C allele in SYBL1 in females with bipolar affective disorder (BPAD) in comparison with controls.
Advani, R. J., Yang, B., Prekeris, R., Lee, K. C., Klumperman, J., Scheller, R. H. VAMP-7 mediates vesicular transport from endosomes to lysosomes. J. Cell Biol. 146: 765-775, 1999. [PubMed: 10459012] [Full Text: https://doi.org/10.1083/jcb.146.4.765]
Ciccodicola, A., D'Esposito, M., Esposito, T., Gianfrancesco, F., Migliaccio, C., Miano, M. G., Matarazzo, M. R., Vacca, M., Franze, A., Cuccurese, M., Cocchia, M., Curci, A. Differentially regulated and evolved genes in the fully sequenced Xq/Yq pseudoautosomal region. Hum. Molec. Genet. 9: 395-401, 2000. [PubMed: 10655549] [Full Text: https://doi.org/10.1093/hmg/9.3.395]
D'Esposito, M., Ciccodicola, A., Gianfrancesco, F., Esposito, T., Flagiello, L., Mazzarella, R., Schlessinger, D., D'Urso, M. A synaptobrevin-like gene in the Xq28 pseudoautosomal region undergoes X inactivation. Nature Genet. 13: 227-229, 1996. [PubMed: 8640232] [Full Text: https://doi.org/10.1038/ng0696-227]
Flowerdew, S. E., Burgoyne, R. D. A VAMP7/Vti1a SNARE complex distinguishes a non-conventional traffic route to the cell surface used by KChIP1 and Kv4 potassium channels. Biochem. J. 418: 529-540, 2009. [PubMed: 19138172] [Full Text: https://doi.org/10.1042/BJ20081736]
Galli, T., Zahraoui, A., Vaidyanathan, V. V., Raposo, G., Tian, J. M., Karin, M., Niemann, H., Louvard, D. A novel tetanus neurotoxin-insensitive vesicle-associated membrane protein in SNARE complexes of the apical plasma membrane of epithelial cells. Molec. Biol. Cell 9: 1437-1448, 1998. [PubMed: 9614185] [Full Text: https://doi.org/10.1091/mbc.9.6.1437]
Mashima, H., Suzuki, J., Hirayama, T., Yoshikumi, Y., Ohno, H., Ohnishi, H., Yasuda, H., Fujita, T., Omata, M. Involvement of vesicle-associated membrane protein 7 in human gastric epithelial cell vacuolation induced by Helicobacter pylori-produced VacA. Infect. Immunity 76: 2296-2303, 2008. [PubMed: 18362137] [Full Text: https://doi.org/10.1128/IAI.01573-07]
Matarazzo, M. R., Cuccurese, M., Strazzullo, M., Vacca, M., Curci, A., Miano, M. G., Cocchia, M., Mercadante, G., Torino, A., D'Urso, M., Ciccodicola, A., D'Esposito, M. Human and mouse SYBL1 gene structure and expression. Gene 240: 233-238, 1999. [PubMed: 10564831] [Full Text: https://doi.org/10.1016/s0378-1119(99)00375-3]
Matarazzo, M. R., De Bonis, M. L., Gregory, R. I., Vacca, M., Hansen, R. S., Mercadante, G., D'Urso, M., Feil, R., D'Esposito, M. Allelic inactivation of the pseudoautosomal gene SYBL1 is controlled by epigenetic mechanisms common to the X and Y chromosomes. Hum. Molec. Genet. 11: 3191-3198, 2002. [PubMed: 12444103] [Full Text: https://doi.org/10.1093/hmg/11.25.3191]
Muller, D. J., Schulze, T. G., Jahnes, E., Cichon, S., Krauss, H., Kesper, K., Held, T., Maier, W., Propping, P., Nothen, M. M., Rietschel, M. Association between a polymorphism in the pseudoautosomal X-linked gene SYBL1 and bipolar affective disorder. Am. J. Med. Genet. 114B: 74-78, 2002. [PubMed: 11840509] [Full Text: https://doi.org/10.1002/ajmg.10115]
Saito, T., Parsia, S., Papolos, D. F., Lachman, H. M. Analysis of the pseudoautosomal X-linked gene SYBL1 in bipolar affective disorder: description of a new candidate allele for psychiatric disorders. Am. J. Med. Genet. 96B: 317-323, 2000. [PubMed: 10898908] [Full Text: https://doi.org/10.1002/1096-8628(20000612)96:3<317::aid-ajmg17>3.0.co;2-r]
Sander, L. E., Frank, S. P. C., Bolat, S., Blank, U., Galli, T., Bigalke, H., Bischoff, S. C., Lorentz, A. Vesicle associated membrane protein (VAMP)-7 and VAMP-8, but not VAMP-2 or VAMP-3, are required for activation-induced degranulation of mature human mast cells. Europ. J. Immun. 38: 855-863, 2008. [PubMed: 18253931] [Full Text: https://doi.org/10.1002/eji.200737634]
Siddiqi, S. A., Mahan, J., Siddiqi, S., Gorelick, F. S., Mansbach, C. M., II. Vesicle-associated membrane protein 7 is expressed in intestinal ER. J. Cell Sci. 119: 943-950, 2006. [PubMed: 16495485] [Full Text: https://doi.org/10.1242/jcs.02803]