PUBLICATION

The function of P-selectin glycoprotein ligand-1 is conserved from ancestral fishes to mammals

Authors
Baïsse, B., Spertini, C., Galisson, F., Smirnova, T., Spertini, O.
ID
ZDB-PUB-190716-4
Date
2019
Source
Journal of Leukocyte Biology   106(6): 1271-1283 (Journal)
Registered Authors
Keywords
adhesion, evolution, sequence
MeSH Terms
  • Humans
  • Cricetulus
  • Amino Acid Sequence
  • Binding Sites
  • Protein Binding
  • Animals
  • Fishes/genetics*
  • Mammals/genetics*
  • Membrane Glycoproteins/chemistry
  • Membrane Glycoproteins/genetics*
  • Membrane Glycoproteins/metabolism
  • Mutation
  • CHO Cells
  • Conserved Sequence
  • Biological Evolution*
  • Protein Interaction Domains and Motifs
  • Amino Acid Motifs
  • Base Sequence
PubMed
31302947 Full text @ J. Leukoc. Biol.
Abstract
PSGL-1 is a mucin-like glycoprotein that supports, in mammals, leukocyte rolling on selectins. However, we have limited knowledge whether its function is conserved in non-mammals and how its structure adapted during evolution. To identify conserved amino acid sequences required for selectin binding, we performed multiple alignments of PSGL-1 sequences from 18 mammals, 4 birds, 3 reptiles, 1 amphibian, and 15 fishes. The amino-terminal T[D/E]PP[D/E] motif, which identifies in mammals a core-2 O-glycosylated threonine required for selectin-binding, is partially conserved in some fishes (e.g., T. rubripes) and birds (e.g., G. gallus), however, most non-mammals do not display it. The sulfated tyrosine residues of human PSGL-1, which bind L- and P-selectin, are not observed in non-mammals, suggesting that they are dispensable for selectin-binding or that other amino acids play their role. A mucin-like domain is present in all species. Interestingly, the alignment of cytoplasmic sequences of non-mammals reveals the conservation of ezrin/radixin/moesin binding site and two new motifs (M1 and M2). To examine the conservation of PSGL-1 function, we cloned PSGL-1 cDNA sequences of zebrafish and fugu, and established their cross-reactivity with human selectins under flow conditions. Importantly, deleting the well-conserved M1 motif strongly decreased PSGL-1 expression at leukocyte surface and induced retention of the precursor molecule in the endoplasmic reticulum, indicating that M1 motif provides a signal required to export PSGL-1 precursors to the Golgi complex. These data show for the first time the conservation of PSGL-1 function from fishes to mammals and reveal the function of a new motif.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping