The diversity of dolichol-linked precursors to Asn-linked glycans likely results from secondary loss of sets of glycosyltransferases. Proc Natl Acad Sci USA

Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, 715 Albany Street, Boston, MA 02118-2932, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 03/2005; 102(5):1548-53. DOI: 10.1073/pnas.0409460102
Source: PubMed

ABSTRACT The vast majority of eukaryotes (fungi, plants, animals, slime mold, and euglena) synthesize Asn-linked glycans (Alg) by means of a lipid-linked precursor dolichol-PP-GlcNAc2Man9Glc3. Knowledge of this pathway is important because defects in the glycosyltransferases (Alg1-Alg12 and others not yet identified), which make dolichol-PP-glycans, lead to numerous congenital disorders of glycosylation. Here we used bioinformatic and experimental methods to characterize Alg glycosyltransferases and dolichol-PP-glycans of diverse protists, including many human pathogens, with the following major conclusions. First, it is demonstrated that common ancestry is a useful method of predicting the Alg glycosyltransferase inventory of each eukaryote. Second, in the vast majority of cases, this inventory accurately predicts the dolichol-PP-glycans observed. Third, Alg glycosyltransferases are missing in sets from each organism (e.g., all of the glycosyltransferases that add glucose and mannose are absent from Giardia and Plasmodium). Fourth, dolichol-PP-GlcNAc2Man5 (present in Entamoeba and Trichomonas) and dolichol-PP- and N-linked GlcNAc2 (present in Giardia) have not been identified previously in wild-type organisms. Finally, the present diversity of protist and fungal dolichol-PP-linked glycans appears to result from secondary loss of glycosyltransferases from a common ancestor that contained the complete set of Alg glycosyltransferases.

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Available from: Daniel J Kelleher, Aug 01, 2015
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    • "The synthesis of the dolichol-linked glycan and its transfer to proteins are identical in both, human cells and C. albicans [3] [4] (see Table 1 and Figure 1). In fact, these processes are quite conserved among eukaryotic cells and there are only a handful of organisms where these stages are slightly different, such as trypanosomatids, some protists, and the fungal pathogen Cryptococcus neoformans [5] [6]. The eukaryotic N-linked glycosylation pathway is divided in two sequential stages: (a) synthesis in the rough endoplasmic reticulum (rER) of the dolichol-linked glycan precursor Dol-PP-GlcNAc 2 Man 9 Glc 3 and its transfer to a nascent protein and (b) the N-linked glycan processing and maturation in the rER and Golgi (Figure 1). "
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    International Journal of Microbiology 07/2014; 2014:267497. DOI:10.1155/2014/267497
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    • "This phenomenon occurs alongside constitutive secretion of non- VSP proteins (Touz et al., 2011), indicating that secretory cargo is trafficked from the ER to distal compartments in the absence of an identifiable intermediate Golgi-like compartment for protein sorting and maturation. This observation complements the lack of complex N-glycosylation in Giardia (Samuelson et al., 2005), a common eukaryotic post-translational modification, suggesting that nonglycosylated proteins could be trafficked directly from their point of synthesis (the ER) to their destination. However, the absence of a bona fide Golgi apparatus in Giardia calls for the presence of alternative sorting and cargo enrichment mechanisms which may rely entirely on the ER, more specifically on ERES. "
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    Cellular Microbiology 10/2012; 15(4). DOI:10.1111/cmi.12054 · 4.82 Impact Factor
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    • "In contrast, confirming the existence of N-glycosylation in the malaria parasite Plasmodium falciparum has proven a difficult task (Davidson and Gowda 2001). Indeed it is known that P. falciparum is missing all of the ALG glycosyltransferases except ALG7 (UDP-N-acetyl- glucosamine-1-phosphotransferase), ALG13 (the second GlcNAc transferase) and the STT3 oligosaccharyltransferase catalytic subunit (Samuelson, et al. 2005). Both P. falciparum and Giardia lamblia are capable of synthesizing Dol-P-P-GlcNAc 2 and transferring this to proteins (Bushkin, et al. 2010, Ratner, et al. 2008). "
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