Human GM3 synthase: a new mRNA variant encodes an NH2-terminal extended form of the protein

Berselli, Patrizia; Zava, Stefania; Sottocornola, E.; Milani, S.; Berra, B.; Colombo, Irma

doi:10.1016/j.bbaexp.2006.07.001

Cited by 22 publications

(18 citation statements)

References 33 publications

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“…On the other hand, GM4 synthase activity was reported to be present in mouse brain (19) and in rat brain and kidney (20). In contrast to previous reports, Berselli et al (21) found that a variant of human GM3 synthase possessing a long N-terminal region utilized not only LacCer but also GalCer as an acceptor substrate. Thus, it is still necessary to clarify which ST or which isoform of ST is responsible for synthesizing GM4 in mammals.…”

Section: Glycosphingolipids (Gsls)contrasting

confidence: 48%

“…3A) (16). Interestingly, a new mRNA variant encodes an N-terminal extended form of hST3GalV that could be expressed in the human placenta and in undifferentiated HL60 cells but not in the monocytic lineage showed broader substrate specificity (21). In this study, we generated three constructs containing cDNA encoding M1-ST3GalV (long form), M2-ST3GalV (middle form), or M3-ST3GalV (short form) of mST3GalV.…”

Section: Discussionmentioning

confidence: 99%

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Zebrafish and Mouse α2,3-Sialyltransferases Responsible for Synthesizing GM4 Ganglioside

Chisada

Yoshimura

Sakaguchi

et al. 2009

Journal of Biological Chemistry

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We have previously reported that fish pathogens causing vibriosis specifically adhere to GM4 on the epithelial cells of fish intestinal tracts (Chisada, S., Horibata, Y., Hama, Y., Inagaki, M., Furuya, N., Okino, N., and Ito, M. (2005) Biochem. Biophys. Res. Commun. 333, 367-373). To identify the gene encoding the enzyme for GM4 synthesis in the fish intestinal tract, a phylogenetic tree of vertebrate ST3GalVs, including Danio rerio and Oryzias latipes, was generated in which two putative subfamilies of fish ST3GalVs were found. Two putative ST3GalVs of zebrafish (zST3GalV-1 and -2), each belonging to different subfamilies, were cloned from the zebrafish cDNA library. Interestingly, zST3GalV-1 synthesized GM3 (NeuAc␣2-3Gal␤1-4Glc␤1-1Cer) but not GM4, whereas zSTGalV-2 synthesized both gangliosides in vitro when expressed in CHO-K1 and RPMI1846 cells. Flow cytometric analysis using anti-GM4 antibody revealed that the transformation of RPMI1846 cells with zST3GalV-2 but not zST3GalV-1 cDNA increased the cell-surface expression of GM4. Whole mount in situ hybridization showed that the zST3GalV-2 transcript was strongly expressed in the gastrointestinal tract, whereas zST3GalV-1 was expressed in the brain and esophagus but not gastrointestinal tract in 3-day post-fertilization embryos. It has long been a matter of controversy which enzyme is responsible for the synthesis of GM4 in mammals. We found that three isoforms of mouse ST3GalV (mST3GalV) having different N-terminal sequences can synthesize GM4 as well as GM3 when expressed in RPMI1846 and CHO-K1 cells. Furthermore, mST3GalV knock-out mice were found to lack GM4 synthase activity and GM4 in contrast to wild-type mice. These results clearly indicate that zST3GalV-2 and mST3GalV are the enzymes responsible for the synthesis of GM4 in zebrafish and mice, respectively.

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Section: Glycosphingolipids (Gsls)contrasting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Zebrafish and Mouse α2,3-Sialyltransferases Responsible for Synthesizing GM4 Ganglioside

Chisada

Yoshimura

Sakaguchi

et al. 2009

Journal of Biological Chemistry

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“…In contrast, human SAT-I transcripts can be classified into three types, hSAT-Ia, -Ib, and -Ic variants, according to the position of transcription initiation, exon 1, 2, or 4 (see Figure 1B; Ishii et al, 1998;Kapitonov et al, 1999;Kim et al, 2001;Berselli et al, 2006). In addition, the structures of hSAT-Ia and -Ib mRNA are each further classified into two types: hSAT-Ia-1 and -Ia-2 variants and hSAT-Ib-1 and -Ib-2 variants, respectively, reflecting alternative splicing of exon 3 ( Figure 1B; Kim et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…According to the first-AUG rule, translation is initiated at the AUG codon nearest the 5Ј end of an mRNA (Kozak, 2002). Thus, in the mSAT-Ib and hSAT-Ic variants, it has been assumed that the first AUG codons, M2 and M2Ј, respectively, are the initiation codons ( Figure 1; Kono et al, 1998;Berselli et al, 2006). However, in the mSAT-Ia, hSAT-Ia-1 and -Ia-2, and hSAT-Ib-1 and -Ib-2 variants, a second or third AUG, M3, has been considered as the initiation codon, based on speculation that the context presenting M1 and M2 is insufficient for either to be recognized by the ribosome as an initiation codon (Ishii et al, 1998;Kapitonov et al, 1999;Kim et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

The Cytoplasmic Tail of GM3 Synthase Defines Its Subcellular Localization, Stability, and In Vivo Activity

Uemura

Yoshida

Shishido

et al. 2009

MBoC

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GM3 synthase (SAT-I) is the primary glycosyltransferase responsible for the biosynthesis of ganglio-series gangliosides. In this study, we identify three isoforms of mouse SAT-I proteins, named M1-SAT-I, M2-SAT-I, and M3-SAT-I, which possess distinct lengths in their NH 2 -terminal cytoplasmic tails. These isoforms are produced by leaky scanning from mRNA variants of mSAT-Ia and mSAT-Ib. M2-SAT-I and M3-SAT-I were found to be localized in the Golgi apparatus, as expected, whereas M1-SAT-I was exclusively found in the endoplasmic reticulum (ER). Specific multiple arginines (R) arranged in an R-based motif, RRXXXXR necessary for ER targeting, were found in the cytoplasmic tail of M1-SAT-I, and in vivo GM3 biosynthesis by M1-SAT-I was very low because of restricted transport to the Golgi apparatus. In addition, M1-SAT-I and M3-SAT-I had a long half-life relative to M2-SAT-I. This is the first report demonstrating the presence of an ER-targeting R-based motif in the cytoplasmic tail of a protein in the mammalian glycosyltransferase family of enzymes. The system, which produces SAT-I isoforms having distinct characteristics, is likely to be of critical importance for the regulation of GM3 biosynthesis under various pathological and physiological conditions.

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“…To understand the global effect of the knockdown genes at the cell level, we performed immunoblot studies to understand the interrelationship between the ciliary and cytoplasmic proteins. In particular, Bicc-1 [36], GM3S [38] and PC2 [39] have been detected at the cell body. miRNA-17 (Mir-17) was included in this experiment, because Mir-17 has been known to modulate PC2 and Bicc-1 [36].…”

Section: Resultsmentioning

confidence: 99%

Protein composition and movements of membrane swellings associated with primary cilia

Mohieldin

Haymour

et al. 2015

Cell. Mol. Life Sci.

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Dysfunction of many ciliary proteins has been linked to a list of diseases, from cystic kidney to obesity and from hypertension to mental retardation. We previously proposed that primary cilia are unique communication organelles that function as microsensory compartments that house mechanosensory molecules. Here we report that primary cilia exhibit membrane swellings or ciliary bulbs, which based on their unique ultrastructure and motility, could be mechanically regulated by fluid-shear stress. Together with the ultrastructure analysis of the swelling, which contains monosialodihexosylganglioside (GM3), our results show that ciliary bulb has a distinctive set of functional proteins, including GM3 synthase (GM3S), bicaudal-c1 (Bicc1), and polycystin-2 (PC2). In fact, results from our cilia isolation demonstrated for the first time that GM3S and Bicc1 are members of the primary cilia proteins. Although these proteins are not required for ciliary membrane swelling formation under static condition, fluid-shear stress induced swelling formation is partially modulated by GM3S. We therefore propose that the ciliary bulb exhibits a sensory function within the mechano-ciliary structure. Overall, our studies provided an important step towards understanding the ciliary bulb function and structure.

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Human GM3 synthase: a new mRNA variant encodes an NH2-terminal extended form of the protein

Cited by 22 publications

References 33 publications

Zebrafish and Mouse α2,3-Sialyltransferases Responsible for Synthesizing GM4 Ganglioside

Zebrafish and Mouse α2,3-Sialyltransferases Responsible for Synthesizing GM4 Ganglioside

The Cytoplasmic Tail of GM3 Synthase Defines Its Subcellular Localization, Stability, and In Vivo Activity

Protein composition and movements of membrane swellings associated with primary cilia

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