Disease relevance of BET1

• Temperature-sensitive mutations in BET1 caused aberrations in cell wall structure, including excretion of alpha-agglutinin into the medium, sensitivity to lysis with Zymolyase and hypersensitivity to Calcofluor White [1].

High impact information on BET1

• The B site binds to Lxx-L/M-E sequences present in both the Bet1 and Sed5 molecules, as well as to the DxE cargo-sorting signal [2].
• We identified a site on Sec24p that recognizes the v-SNARE Bet1p and show that packaging of a number of cargo molecules is disrupted when mutations are introduced at this site [3].
• These vesicles contain Bos1p, Sec22p, and Ypt1p, but not Bet1p [4].
• Furthermore, unlike Sec24p, Lst1p fails to bind to Bet1p in vitro, indicating a direct correlation between cargo binding and recruitment into vesicles [5].
• Vesicles bearing mutations in Bet1p or Bos1p inhibit fusion with wild-type acceptor membranes, but acceptor membranes containing these mutations are fully functional [6].

Biological context of BET1

• The temperature-sensitive phenotype of the uso1-1 mutant can be suppressed by overexpression of each of the known ER to Golgi v-SNAREs (Bet1p, Bos1p, Sec22p, and Ykt6p) [7].
• While screening a yeast genomic library for genes complementing the ER-accumulating mutant bet1 (A. Newman and S. Ferro-Novick, J. Cell Biol. 105: 1587-1594, 1987), we isolated BET1 and BOS1 (bet one suppressor) [8].
• The new mutants, bet1 and bet2, are temperature sensitive for growth and protein transport [9].
• SLY12 but not SLY41 is an essential gene [10].
• Sequence analysis revealed the presence of 17 open reading frames (ORFs), four of them previously known yeast genes (sly12, pan1, sts1 and prl1), a tRNA gene and the centromere motif [11].

Anatomical context of BET1

• BOS1 and BET1 are required for transport from the ER to the Golgi complex in yeast and genetically interact with each other and a subset of the other genes, whose products function at this stage of the secretory pathway [12].
• Bos1p co-purifies with the ER to Golgi transport vesicles and co-fractionates with Bet1p and the ER membrane [12].
• We previously identified BET3 by its genetic interactions with BET1, a gene whose SNARE-like product acts in endoplasmic reticulum (ER)-to-Golgi transport [13].
• Among mutants that were temperature-sensitive for growth and for ability to cross-link the mannoprotein alpha-agglutinin to the cell wall, one strain was complemented by BET1, which encodes an ER-Golgi v-SNARE [1].
• SLY2 and SLY12 encode proteins with hydrophobic tails similar to synaptobrevins, integral membrane proteins of synaptic vesicles in higher eucaryotes [10].

Associations of BET1 with chemical compounds

• Expression of SNARE cysteine derivatives in the same strain produced a cross-linked heterodimer of Bet1p and Sec22p under oxidizing conditions [14].
• In wild-type parental or bet1 cells, secretion of alpha-agglutinin also continued after protein synthesis was blocked with cycloheximide [1].

Regulatory relationships of BET1

• Bet1p activates the v-SNARE Bos1p [15].

Other interactions of BET1

• Thus, this set of SNARE proteins is symmetrically distributed between vesicle and acceptor compartments, but they function asymmetrically such that Bet1p and Bos1p are required on vesicles and Sed5p activity is required on acceptor membranes [6].
• Deletion of ISS1 had no significant effect on growth or secretion; however, iss1Delta mutants were found to be synthetically lethal with mutations in the v-SNARE genes SEC22 and BET1 [16].
• Overexpression of SLY12 compensates for the loss of function of the ras-like GTP-binding protein Ypt1 [12].
• Overexpression of two of them, BET1p and Sec22p, can also suppress the lethality of delta uso1, indicating that the SNAREs function downstream of Uso1p [7].
• An analysis of BET1, BET2, and BOS1. Three factors mediating ER to Golgi transport in yeast [17].

Analytical, diagnostic and therapeutic context of BET1

• The data obtained by monitoring of Kex2p cleavage, by immunofluorescence microscopy and cell fractionation showed that Bos1-alpha and Bet1-alpha have different cellular localization and dynamics [18].
• Quantitative Western blot analysis indicates that protein markers of cytosol and cellular membranes are depleted throughout the purification, whereas the synaptobrevin-like Bet1, Sec22, and Bos1 proteins are highly enriched [19].
• Mutational analysis points to the coiled-coil region as necessary for Bet1p function, and circular dichroism experiments support this theory [15].

References