In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 106, No. 6 ( 2019-11-28), p. 1271-1283
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.
Type of Medium:
Online Resource
ISSN:
1938-3673
,
0741-5400
DOI:
10.1002/JLB.2A0818-327RR
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2019
detail.hit.zdb_id:
2026833-6
SSG:
12
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