Disease relevance of STE1

• Escherichia coli extracts, obtained from a strain expressing the Arabidopsis SMT1 protein, can perform both the methyl and ethyl additions to appropriate sterol substrates, although with different kinetics [1].
• Lesions in the sterol delta reductase gene of Arabidopsis cause dwarfism due to a block in brassinosteroid biosynthesis [2].
• WT plants treated exogenously with inhibitors of sterol biosynthesis had similar gene expression and sterility characteristics as the hmg1 mutants [3].

High impact information on STE1

• They do so by altering the predicted sterol/lipid-binding domains of ATHB14 and ATHB9, proteins of previously unknown function that also contain DNA-binding motifs [4].
• FK encodes a predicted integral membrane protein related to the vertebrate lamin B receptor and sterol reductases across species, including yeast sterol C-14 reductase ERG24 [5].
• Although fk represents a sterol biosynthetic mutant, the phenotype was not rescued by feeding with brassinosteroids (BRs), the only plant sterol signaling molecules known so far [5].
• We propose that synthesis of sterol signals in addition to BRs is important in mediating regulated cell growth and organization during embryonic development [5].
• Furthermore, auxin transport inhibitors and interference with the sterol composition of membranes disrupt polar AUX1 distribution at the plasma membrane [6].

Biological context of STE1

• Thus, the reduction of BRs in dwf7 is due to a shortage of substrate sterols and is the direct cause of the dwarf phenotype in dwf7 [7].
• Sequencing of the STE1 locus in two dwf7 mutants revealed premature stop codons in the first (dwf7-2) and the third (dwf7-1) exons [7].
• Molecular genetics of plant sterol backbone synthesis [8].
• The orc mutant was identified originally by defects in root patterning, and positional cloning revealed that the affected gene encodes STEROL METHYLTRANSFERASE1, which is required for the appropriate synthesis and composition of major membrane sterols. smt1(orc) mutants displayed several conspicuous cell polarity defects [9].
• The fact that smt1 null mutants still produce alkylated sterols and that SMT1 can catalyze both alkylation steps shows that there is considerable overlap in the substrate specificity of enzymes in sterol biosynthesis [1].

Anatomical context of STE1

• This indicates that PSAT both regulates the pool of free sterols as well as limits the amount of free sterol intermediates in the membranes [10].
• Our results reveal sterol-enriched early endosomes as targets for BFA interference in plants [11].
• Similar to animals, biosynthetic sterol transport occurs from the endoplasmic reticulum (ER) via the Golgi apparatus to the plasma membrane [11].
• The trafficking and function of cell surface proteins in eukaryotic cells may require association with detergent-resistant sphingolipid- and sterol-rich membrane domains [12].
• A link between sterol biosynthesis, the cell wall, and cellulose in Arabidopsis [13].

Associations of STE1 with chemical compounds

• The Arabidopsis dwf7/ste1 mutant is defective in the delta7 sterol C-5 desaturation step leading to brassinosteroid biosynthesis [7].
• Feeding studies with BR biosynthetic intermediates and analysis of endogenous levels of BR and sterol biosynthetic intermediates indicate that the defective step in dwf7-1 resides before the production of 24-methylenecholesterol in the sterol biosynthetic pathway [7].
• Transformants (4 x 10(5)) were screened for cycloheximide (CH) resistance and 400 possible clones were analyzed to determine their sterol profile [14].
• We propose a model in which correct sterol profiles are required for regulated auxin and ethylene signaling through effects on membrane function [15].
• The smt1 plants have pleiotropic defects: poor growth and fertility, sensitivity of the root to calcium, and a loss of proper embryo morphogenesis. smt1 has an altered sterol content: it accumulates cholesterol and has less C-24 alkylated sterols content [1].

Physical interactions of STE1

• CONCLUSIONS: Early endocytic sterol trafficking involves transport via ARA6-positive early endosomes that, in contrast to animal cells, is actin dependent [11].

Enzymatic interactions of STE1

• Squalene synthase (SQS) catalyzes the first committed step of the sterol biosynthetic pathway [16].
• The AtPSAT is the only intracellular enzyme found so far that catalyzes an acyl-CoA-independent sterol ester formation [10].

Other interactions of STE1

• The sterol levels in hmg1 mutants were lower than in the WT [3].
• We identified CVP1 and found that it encodes STEROL METHYLTRANSFERASE2 (SMT2), an enzyme in the sterol biosynthetic pathway [17].
• SMT2 and the functionally redundant SMT3 act at a branch point in the pathway that mediates sterol and brassinosteroid levels [17].
• Cloning and characterization of the Arabidopsis thaliana SQS1 gene encoding squalene synthase--involvement of the C-terminal region of the enzyme in the channeling of squalene through the sterol pathway [16].
• Biochemical analysis indicates that the fk-J79 mutation results in deficient C-14 sterol reductase activity, abnormal sterol composition, and reduction of brassinosteroids (BRs) [18].

Analytical, diagnostic and therapeutic context of STE1

• The mutant STE 1 was isolated by screening an ethylmethane sulfonate (EMS)-mutagenized population of Arabidopsis thaliana which consisted of 22,000 M2 plants divided into 1100 pools of 20 plants by gas chromatography of sterols extracted from small leaf samples [19].
• Sequence analysis reveals that Sop2, tentatively named steroleosin, possesses a hydrophobic anchoring segment preceding a soluble domain homologous to sterol-binding dehydrogenases/reductases involved in signal transduction in diverse organisms [20].
• We used protein modelling and site-directed mutagenesis to investigate why the BODIPY-PC transfer mediated by E. lagascae SCP-2 is not sensitive to sterols, whereas the transfer mediated by A. thaliana SCP-2 shows sterol sensitivity [21].

References