Evidence map›Paper›PMID 32845322›Full record

ArticleGlycobiology2021

Human-specific microglial Siglec-11 transcript variant has the potential to affect polysialic acid-mediated brain functions at a distance.

Masaya Hane, Dillon Y Chen, Ajit Varki

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Glycobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. Sialylation in the nervous system: Functions and mechanisms.The Journal of biological chemistry · 2026
    Review
  4. Review
  5. Siglecs: From Biomodulation to Immunotherapy.Current protein & peptide science · 2026
    Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Siglec Ligands.Cells · 2021
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Masaya HaneDepartments of Medicine and Cellular & Molecular Medicine, Center for Academic Research and Training in Anthropogeny, Glycobiology Research and Training Center, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA.
Dillon Y ChenDepartments of Medicine and Cellular & Molecular Medicine, Center for Academic Research and Training in Anthropogeny, Glycobiology Research and Training Center, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA.
Ajit VarkiDepartments of Medicine and Cellular & Molecular Medicine, Center for Academic Research and Training in Anthropogeny, Glycobiology Research and Training Center, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA.
University of California, San Diego · US

Funding

BIOSYNTHESIS AND REGULATION OF SUBSTITUTED SIALIC ACIDSR01GM032373 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VARKI, AJIT P · 1985 to 2022
$6.9M
UCSD Biomedical Scientist Career Development Program in GlycoscienceK12HL141956 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D, GODULA, KAMIL · 2018 to 2022
$5.3M
NHLBI NIH HHS K12 HL141956NIGMS NIH HHS R01 GM032373
6 · The paper itself

Abstract

CD33-related Siglecs are often found on innate immune cells and modulate their reactivity by recognition of sialic acid-based "self-associated molecular patterns" and signaling via intracellular tyrosine-based cytosolic motifs. Previous studies have shown that Siglec-11 specifically binds to the brain-enriched polysialic acid (polySia/PSA) and that its microglial expression in the brain is unique to humans. Furthermore, human microglial Siglec-11 exists as an alternate splice form missing the exon encoding the last (fifth) Ig-like C2-set domain of the extracellular portion of the protein, but little is known about the functional consequences of this variation. Here, we report that the recombinant soluble human microglial form of Siglec-11 (hSiglec-11(4D)-Fc) binds endogenous and immobilized polySia better than the tissue macrophage form (hSiglec-11(5D)-Fc) or the chimpanzee form (cSiglec-11(5D)-Fc). The Siglec-11 protein is also prone to aggregation, potentially influencing its ligand-binding ability. Additionally, Siglec-11 protein can be secreted in both intact and proteolytically cleaved forms. The microglial splice variant has reduced proteolytic release and enhanced incorporation into exosomes, a process that appears to be regulated by palmitoylation of cysteines in the cytosolic tail. Taken together, these data demonstrate that human brain specific microglial hSiglec-11(4D) has different molecular properties and can be released on exosomes and/or as proteolytic products, with the potential to affect polySia-mediated brain functions at a distance.

Indexed as

BrainHumansLectinsMembrane ProteinsProtein IsoformsSialic AcidsLectinsMembrane Proteinspolysialic acidProtein IsoformsSialic AcidsSIGLEC11 protein, humanexosomepolysialic acidprotein palmitoylationSiglec-11

Identifiers

PMID32845322
PMCPMC8022978
OpenAlexW3080543750

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.