Disease relevance of SYBL1

• We have previously shown that the amino-terminal Longin domain of the v-SNARE TI-VAMP (tetanus neurotoxin-insensitive vesicle-associated membrane protein)/VAMP7 plays an inhibitory role in neurite outgrowth [1].

Psychiatry related information on SYBL1

• Association between a polymorphism in the pseudoautosomal X-linked gene SYBL1 and bipolar affective disorder [2].

High impact information on SYBL1

• Unlike all Xp PAR genes studied so far, a synaptobrevin-like gene, tentatively named SYBL1, undergoes X inactivation [3].
• The functions and cellular localization of longins are regulated at several levels and the longin prototypes TI-VAMP, Sec22 and Ykt6 show different distributions among eukaryotes, reflecting their modular and functional diversity [4].
• VAMP-7 mediates vesicular transport from endosomes to lysosomes [5].
• These data are consistent with a role for VAMP-7 in the vesicular transport of proteins from the early endosome to the lysosome [5].
• Treatment with nocodozole or brefeldin A does not disrupt the colocalization of VAMP-7 and LAMP-1 [5].

Biological context of SYBL1

• Although it is unclear at present how this allele-specific silencing comes about, the data also indicate that the epigenetic features of the 'Y inactivation' of SYBL1 are mechanistically similar to those associated with X-chromosome inactivation [6].
• Combined, our data suggest that specific combinations of histone methylation and acetylation are involved in the somatic maintenance of permissive and repressed chromatin states at SYBL1 [6].
• In ICF syndrome, a human disease affecting DNA methylation, SYBL1 escapes from silencing and this correlates with altered patterns of histone methylation and acetylation [6].
• Allelic inactivation of the pseudoautosomal gene SYBL1 is controlled by epigenetic mechanisms common to the X and Y chromosomes [6].
• Band shift and transient reporter gene assays indicate a strong role of two of these evolutionary conserved regions in regulating SYBL1 transcription [7].

Anatomical context of SYBL1

• The results reported here clarify that a Staf-zinc finger family factor, together with the CAAT factor, is the major nuclear protein bound to the SYBL1 promoter region and is responsible for its regulation in HeLa cells, thus identifying the basic control of SYBL1 transcription [7].
• SYBL1, which maps to the Xq pseudoautosomal region (PAR), encodes a member of the synaptobrevin family of proteins involved in synaptic vesicle docking, exocytosis, and membrane transport [2].
• So far, only one SNARE, VAMP7, has been localized to late endosomes (LEs), where it is proposed to mediate trafficking of epidermal growth factor receptor to LEs and lysosomes [8].
• In epithelial cells, TI-VAMP-containing vesicles were concentrated in the apical domain, and the protein was detected at the apical plasma membrane by immunogold labeling on ultrathin cryosections [9].
• Antibodies to syntaxin 8 and a soluble recombinant VAMP7 fragment both inhibit in vitro reconstituted D. discoideum endosome fusion [10].

Associations of SYBL1 with chemical compounds

• However, RNA interference of endogenous MECP2 does not induce the expression of the inactive SYBL1 alleles, suggesting that its silencing activity can be replaced by the other methyl-binding proteins [11].
• Immunoelectron microscopy analysis shows that VAMP-7 is most concentrated in the trans-Golgi network region of the cell as well as late endosomes and transport vesicles that do not contain the mannose-6 phosphate receptor [5].
• First, it negatively regulates the ability of TI-VAMP and of a Longin/Synaptobrevin chimera to participate in SNARE complexes [1].
• The nascent allergen-containing phagosomes were found to transform into granule compartments by acquiring VAMP7 and serotonin and exhibited the capacity to empty their contents upon mast cell activation [12].
• Anti-VAMP7 antibodies reduced the transfer of triacylglycerol, but not newly synthesized proteins, from the ER to the Golgi by 85% [13].

Regulatory relationships of SYBL1

• Redistribution of TI-VAMP in the ER of syntaxin-1-expressing cells was microtubule dependent and impaired the trafficking of CD63, a cargo of TI-VAMP-containing vesicles [14].
• Furthermore, we report that Cdc42 activates exocytosis of pHLuorin tagged TI-VAMP in an actin-dependent manner [15].
• We report that MT1-MMP-dependent matrix degradation at invadopodia is regulated by the v-SNARE TI-VAMP/VAMP7, hence providing the molecular inventory mediating focal degradative activity of cancer cells [16].

Other interactions of SYBL1

• We suggest that TI-VAMP, SNAP23, and syntaxin 3 can participate in exocytotic processes at the apical plasma membrane of epithelial cells and, more generally, domain-specific exocytosis in clostridial NT-resistant pathways [9].
• Recent findings show that, like XpPAR genes, IL9R escapes X inactivation and its Y allele is also expressed, but SYBL1 seems to act like an X-linked gene, expressed from the active X chromosome but not from the inactive X or Y [17].
• The relatively stable maintenance of SPRY3 silencing compared with SYBL1 suggests that genes without CpG islands may be less prone to reactivation than previously thought and that genes with CpG islands require promoter methylation as an additional layer of repression [18].
• We studied the methylation pattern of the promoters of two X chromosomal genes, G6 PD and SYBL1, in patients with RTT and in a control group [19].
• We observed that in vitro methylation of either the SYBL1 or the GPC3 promoter resulted in repression of reporter constructs [20].

Analytical, diagnostic and therapeutic context of SYBL1

• In vivo binding of Staf proteins to the SYBL1 promoter is confirmed by chromatin immunoprecipitation assays [7].
• VAMP7 was concentrated on intestinal ER by immunofluorescence microscopy [13].
• Iodixanol gradient centrifugation showed VAMP7 to be isodense with ER and endosomes [13].
• BACKGROUND: This study characterizes two long vesicle-associated membrane protein (VAMP) genes (SYBL-1 and SYBL-2) obtained from DNA of Entamoeba histolytica by PCR amplification [21].

References