Disease relevance of DPM1

• DPM1 is the structural gene for yeast Dol-P-Man synthase since Escherichia coli transformants harboring this gene express Dol-P-Man synthase activity in vitro [1].
• This intermediate was previously shown to accumulate, however, in murine lymphoma mutant E and in yeast mutant dpm1, both of which lack dolicholphosphomannose synthase activity [2].

High impact information on DPM1

• Here, we show that a COOH-terminal region in yeast Sac1p is crucial for ER targeting by directly interacting with dolicholphosphate mannose synthase Dpm1p [3].
• DPM2 regulates biosynthesis of dolichol phosphate-mannose in mammalian cells: correct subcellular localization and stabilization of DPM1, and binding of dolichol phosphate [4].
• DPM2, an 84 amino acid membrane protein expressed in the endoplasmic reticulum (ER), makes a complex with DPM1 that is essential for the ER localization and stable expression of DPM1 [4].
• (ii) The ALG7 and DPM1 proteins are known to recognize the isoprenoid region of dolichol phosphate specifically; this recognition presumably occurs in the membrane since dolichol is very hydrophobic [5].
• We present evidence that the S. cerevisiae gene DPM1, when stably transfected into a mutant Chinese hamster ovary cell line, B4-2-1, is able to correct the glycosylation defect of the cells [6].

Biological context of DPM1

• Pathway activation was also suppressed in dpm1-101 mutants by plasmids that contained RER2 or PSA1, which produce the substrates for Dpm1 [7].
• The possibility that cloned cDNA encodes a product with a MPD synthase activity was also excluded by transforming a heterozygous S. cerevisiae dpm1::LEU2/DPM1 diploid, which did not lead to the restoration of viability of the dpm1 spores [8].
• Temperature-sensitive yeast mutants were isolated after in vitro mutagenesis of the yeast DPM1 gene [9].
• Instead, DPM1 may be an essential gene because its product is required for O-glycosylation in yeast or because Dol-P-Man synthase is needed in some unidentified pathway [1].
• DNA sequencing of the DPM1 gene revealed an open reading frame of 801 bases [1].

Anatomical context of DPM1

• Indirect immunofluorescence with a primary antibody directed against the DPM1 protein shows a reticular staining pattern of protein localization in transfected hamster and monkey cell lines [6].
• Electron microscopy of the DPM1-amplified strains revealed amorphous structure of the cell wall and over three times as many mitochondria as in the control [10].
• Four stable transformants, each with different copy numbers of tandemly integrated DPM1, exhibited roughly double the activity of MPD synthase in the respective endoplasmic reticulum membrane fraction [10].
• A comparison of protein secretion from protoplasts with that from mycelia showed that the cell wall created a barrier for secretion in the DPM1 transformants [11].
• Overexpression of the yeast DPM1 gene encoding dolichylphosphate mannose synthase (DPMS) in an Aspergillus nidulans mutant (BWB26A) deficient in O-glycosylation caused an increase in the number of secretory vesicles and changes in protein secretion [12].

Associations of DPM1 with chemical compounds

• Genomic DNAs from several fungi were screened for a homologous sequence to Saccharomyces cerevisiae DPM1, an essential gene which encodes dolichyl phosphoryl mannose synthase [13].
• We analysed the translocation of the Dolichol-phosphate-mannose synthase into dog pancreatic microsomal membranes: resistance to proteolytic attack provides evidence of its luminal orientation and asks for a reevaluation of the topology of the reaction [14].

Other interactions of DPM1

• The ALG5 protein has sequence similarity to the GDP-mannose:dolichyl-phosphate mannosyltransferase (Dpm1p) from S. cerevisiae [15].
• The interaction with Dpm1p persists during exponential cell division but is rapidly abolished when cell growth slows because of nutrient limitation, causing translocation of Sac1p to Golgi membranes [3].
• The secretion mutant sec59 has a similar phenotype to dpm1, and the presence of a dolichol recognition sequence in the SEC59 protein gave a clue to its defect, which is in dolichol kinase [16].

Analytical, diagnostic and therapeutic context of DPM1

• Expression of dolichol phosphate mannose synthase of S. mansoni (SmDPMS) was analysed by Northern blot and quantified by semi-quantitative RT-PCR with cDNA from mature and immature male and female worms [17].
• SDS/ PAGE of the purified enzyme fraction revealed the presence of a protein band of 31 kDa corresponding to the apparent molecular mass of the MPD-synthase purified from S. cerevisiae [Babczinski, P. et al. (1980) Eur. J. Biochem. 105, 509-515; Haselbeck A. (1989) Eur. J. Biochem. 181, 663-668] [18].

References