| 2014 |
SLC35A1 deficiency impairs α-dystroglycan O-mannosylation independently of sialic acid; lentiviral complementation with disease mutation p.Q101H failed to restore O-mannosylation in SLC35A1 knockout cells but partly restored sialylation, demonstrating a role for SLC35A1 in α-DG O-mannosylation distinct from its CMP-sialic acid transport function. |
SLC35A1-knockout cell model (HAP1), lentiviral complementation with wild-type and p.Q101H mutant, α-DG ligand-binding assay, sialic acid incorporation assay |
Human molecular genetics |
High |
25552652
|
| 2020 |
CDG-causing mutations Q101H, T156R, and E196K differentially impair SLC35A1 transporter function and dimer formation; all mutants retain correct Golgi localization. Single T156R and E196K mutants partially restore sialylation in CST-deficient HEK293T cells, whereas the compound T156R/E196K combination strongly reduces functionality, and differences in dimer formation capacity were observed among variants. |
Expression of mutant SLC35A1 variants in CST-deficient HEK293T cells, lectin staining, N- and O-glycan MS analysis, glycolipid analysis, microscopy for Golgi localization, dimer formation assay |
International journal of molecular sciences |
Medium |
33396746
|
| 2021 |
SLC35A1 transports CDP-ribitol into the Golgi in addition to CMP-sialic acid; the large binding pocket of SLC35A1 accommodates both substrates. Introducing bulky residues from SLC35A4 into the SLC35A1 binding pocket abolished sialylation but retained CDP-ribitol transport and ribitol phosphorylation of α-dystroglycan, demonstrating that binding-pocket size determines substrate specificity and that SLC35A1 and SLC35A4 redundantly transport CDP-ribitol. |
Site-directed mutagenesis of SLC35A1 binding pocket, expression in SLC35A1 KO cell lines, sialylation assay, ribitol phosphorylation assay of α-dystroglycan |
The Journal of biological chemistry |
High |
34015330
|
| 2021 |
Megakaryocyte/platelet-specific deletion of Slc35a1 in mice causes thrombocytopenia through two mechanisms: impaired megakaryocyte maturation in bone marrow and accelerated clearance of desialylated platelets by Kupffer cells in the liver. |
Conditional Slc35a1 knockout mice (Plt Slc35a1−/−), bone marrow megakaryocyte analysis, platelet count, liver histology, lectin staining for desialylation |
Haematologica |
High |
32303557
|
| 2022 |
SLC35A1 physically associates with the α2,3-sialyltransferase ST3Gal4 in the Golgi; this interaction is disrupted by the CDG-causing E196K mutation (but not T156R), and the E196K mutant is less efficient at restoring N-glycan sialylation in SLC35A1-KO cells, suggesting the transporter–sialyltransferase complex is functionally important for N-glycan sialylation. |
Co-immunoprecipitation of SLC35A1 with ST3Gal4, expression of CDG mutants (E196K, T156R) in SLC35A1-KO cells, lectin/glycan analysis of N-glycan sialylation |
Biochemical and biophysical research communications |
Medium |
36257191
|
| 2024 |
Endothelial-specific Slc35a1 deletion in mice causes desialylation of VEGFR2 in liver sinusoidal endothelial cells (LSECs), leading to enhanced VEGFR2 signaling, sinusoidal capillarization, disrupted hepatic zonation, and excessive neonatal lipid deposition; pharmacological inhibition of VEGFR2 with SU5416 rescued lipid deposition and hepatic vasculature, placing SLC35A1-mediated sialylation upstream of VEGFR2 signaling in LSEC identity. |
Endothelial-specific Slc35a1 knockout mice, immunofluorescence, immunoblot, RNA sequencing, lipidomic profiling, VEGFR2 signaling analysis, SU5416 pharmacological rescue |
Cellular and molecular gastroenterology and hepatology |
High |
38467191
|
| 2021 |
Knockout of SLC35A1 in HEK293T and HeLa cells eliminates cell-surface sialic acid, thereby unmasking terminal galactose residues and rendering cells permissive to AAV9 transduction, demonstrating that SLC35A1-dependent sialylation masks the galactose-based AAV9 receptor on these cells. |
CRISPR/Cas9 KO of SLC35A1 in HEK293T and HeLa cells, AAV9 transduction assay, lectin staining for cell-surface sialic acid and galactose |
Cells |
Medium |
34069698
|
| 2024 |
SLC35A1 KO reduces α2,6-linked sialic acid expression and impairs nuclear import of multiple rAAV serotypes post-internalization; deletion of the C-terminal cytoplasmic tail of SLC35A1 significantly decreases rAAV transduction and vector nuclear import without drastically reducing sialic acid expression, while the T128A mutant reduces sialic acid but still supports rAAV transduction, indicating the C-tail has a sialylation-independent role in rAAV intracellular trafficking. |
Genome-wide CRISPR/Cas9 KO screen, SLC35A1 KO and domain-deletion/point-mutant (ΔC-tail, T128A) cell lines, rAAV transduction assays across multiple serotypes, flow cytometry for surface sialic acid, nuclear import assay |
mBio |
Medium |
39601564
|
| 2022 |
SLC35A1 KO in LLC-PK1 cells reduces cell-surface sialic acid and decreases porcine deltacoronavirus (PDCoV) adsorption; trypsin treatment promotes SA-dependent PDCoV entry. The T182 residue in the PDCoV S1 N-terminal domain was identified as a putative SA-binding site, placing SLC35A1-mediated sialylation at the viral attachment step. |
Genome-wide CRISPR/Cas9 KO screen in LLC-PK1 cells, SLC35A1 KO validation, viral adsorption assay, recombinant PDCoV with S1 domain mutations, trypsin treatment, lectin staining |
Journal of virology |
Medium |
36453883
|
| 2019 |
Loss of SLC35A1 (the sialic acid transporter) affects cell survival upon VSV infection and modulates the apoptotic response induced by VSV, implicating SLC35A1 in the host apoptotic response to oncolytic virus infection. |
Focused CRISPR/Cas9 KO library genetic screen for cell survival upon VSV infection, follow-up characterization of SLC35A1 KO cells |
Scientific reports |
Low |
31320712
|
| 2025 |
The SLC35A1 p.Thr45Ala disease variant does not directly impair CMP-Neu5Ac transport (as restoration of CMP-Neu5Ac levels was achieved in KO cells transfected with the variant), but causes reduced protein stability (~65% residual activity), leading to impaired sialylation of ICAM1, GP130, and TGN46, altered N-glycans, and secondary effects on O-GlcNAcylation, energy, and lipid metabolism. |
CRISPR/Cas9 SLC35A1 KO HEK293 cells complemented with WT or p.Thr45Ala variant, CMP-Neu5Ac measurement, lectin staining, LC-MS N-glycan analysis, immunoblot, patient fibroblast analysis, GlcNAc supplementation rescue |
Human mutation |
Medium |
40613041
|