Disease relevance of FLO1

• Southern blots and genetic crosses showed that the URA3 gene had integrated at the expected position on chromosome I. A region of approximately 2 kb in the middle of the FLO1 gene was consistently deleted during propagation in Escherichia coli and could not be isolated [1].
• Here bacterial carboxylesterase EstA from Burkholderia gladioli was covalently anchored into the cell wall of Saccharomyces cerevisiae by in-frame fusion to the endogenous yeast proteins Kre1p, Cwp2p, and Flo1p [2].

High impact information on FLO1

• These terminally repetitive regions consist of a telomeric repeat called W', flanked by DNA closely related to the yeast FLO1 gene [3].
• Both pathways contribute to modulate the expression of the MUC1/FLO11 gene which encodes a cell-surface flocculin required for pseudohyphal and invasive growth [4].
• PKA signals pseudohyphal growth, in part, by regulating Flo8-dependent expression of the cell surface flocculin Flo11 [5].
• FLO11 encodes a cell surface flocculin with a structure similar to the class of yeast serine/threonine-rich GPI-anchored cell wall proteins [6].
• We report here that the Gpr1 receptor is required for filamentous and haploid invasive growth and regulates expression of the cell surface flocculin Flo11 [7].

Biological context of FLO1

• Until now only the FLO1 gene, which is located at chromosome I, has been cloned and sequenced [8].
• The phenotype was suppressed by a single gene of wide distribution among non-flocculent strains (proposed as fsu3) that, however, was unable to suppress other FLO1 genes in other flocculent strains [9].
• The flocculation character in strain IM1-8b of Saccharomyces cerevisiae is controlled by a single and dominant gene shown to be allelic to FLO1 [9].
• The intact FLO1 gene was then cloned and its nucleotide sequence determined [10].
• Sequence of the open reading frame of the FLO1 gene from Saccharomyces cerevisiae [11].

Anatomical context of FLO1

• FLO1 may govern the expression of a proteinaceous, lectin-like activity, firmly associated with the cell walls of flocculent cells, which bind to the alpha-mannan carbohydrates of adjoining cells [12].
• S. cerevisiae expressing either of two flocculation phenotypes, Flo1 or NewFlo, adhered to endothelial cells as avidly as did yeasts expressing CAD1/AAF1 [13].
• We have assessed the localization of Flo1p by immunoelectron microscopy, and in this study we show that this protein is located in the external mannoprotein layer of the cell wall, at the plasma membrane level and in the periplasm [14].
• The membranous forms of Flo1p were shown to be solubilized by phosphatidylinositol-phospholipase C treatment, suggesting that Flo1p is glycosyl phosphatidylinositol (GPI) anchored to this organelle [14].

Associations of FLO1 with chemical compounds

• It is proposed that this indicates two entirely distinct mechanisms of flocculation, probably involving a mannose-specific lectin in the FLO 1 type and a broad specificity lectin in the NewFLO type [15].
• The Saccharomyces cerevisiae FLO1 gene encodes a large 1,536-amino-acid serine- and threonine-rich protein involved in flocculation [14].
• The flocculent phenotypes conferred by both the FLO1 and the FLO5 gene were irreversibly lost upon treatment with pronase, proteinase K, trypsin or 2-mercaptoethanol treatments [16].
• Flo1p was extracted from cell walls in large amounts by boiling in sodium dodecyl sulfate, suggesting that it is noncovalently anchored to the cell wall network [14].
• Disruption of the Nrg1p-repressed gene FLO11, which encodes a cell surface glycoprotein that functions as a flocculin or an adhesin, abolished flor formation [17].

Regulatory relationships of FLO1

• Herein, we report that the GTS1-induced flocculation was flocculin-dependent in nature and was caused by expression of the major flocculin Flo1p [18].
• For example, a strain expressing FLO1 under control of the JEN1 promoter flocculates at a low glucose concentration [19].

Other interactions of FLO1

• The sequencing of a 6619 bp region encoding for a flocculation gene previously cloned from a strain defined as FLO5 (Bidard et al., 1994) has revealed that it was a FLO1 gene [20].
• It is thought that the FLO8 gene encodes a transcriptional activator of the dominant flocculation gene FLO1 in Saccharomyces cerevisiae [21].
• The FLO11-encoded flocculin is required for a variety of important phenotypes in Saccharomyces cerevisiae, including flocculation, adhesion to agar and plastic, invasive growth, pseudohyphae formation and biofilm development [22].
• Disruption of the FLO1 gene in the tup1 and ssn6 strains showed that one of the transcripts corresponded to the FLO1 gene [23].
• The 3' end of the FLO1 gene was localized at approximately 24 kb from the right end of chromosome I, 20 kb centromere-proximal to PHO11 [1].

Analytical, diagnostic and therapeutic context of FLO1

• However, further study (genomic Southern and polymerase chain reaction analyses) indicated that the gene we cloned was not the intact FLO1 gene but a form with an approximately 2 kb deletion in the ORF region [10].
• Molecular cloning and analysis of the yeast flocculation gene FLO1 [10].
• We have assessed the availability of the Flo proteins at the cell surface during the growth of two flocculent strains, ABXL-1D (FLO1) and STX347-1D (FLO5) using immunological approaches, enzyme-linked immunosorbent assays and immunofluorescence [24].
• A Northern-blot analysis has demonstrated that the same 5000-nt transcript was present in an FLO5 and an FLO1 strain [25].
• After sporulation and dissection of asci, three haploid strains were chosen, which were altered in the locus FLO1 [26].

References