Unique, Polyfucosylated Glycan–Receptor Interactions Are Essential for Regeneration of Hydra magnipapillata

Abstract

Cell-cell communications, cell-matrix interactions, and cell migrations play a major role in regeneration. However, little is known about the molecular players involved in these critical events, especially cell surface molecules. Here, we demonstrate the role of specific glycan-receptor interactions in the regenerative process using Hydra magnipapillata as a model system. Global characterization of the N- and O-glycans expressed by H. magnipapillata using ultrasensitive mass spectrometry revealed mainly polyfucosylated LacdiNAc antennary structures. Affinity purification showed that a putative C-type lectin (accession number Q6SIX6) is a likely endogenous receptor for the novel polyfucosylated glycans. Disruption of glycan-receptor interactions led to complete shutdown of the regeneration machinery in live Hydra. A time-dependent, lack-of-regeneration phenotype observed upon incubation with exogenous fuco-lectins suggests the involvement of a polyfucose receptor-mediated signaling mechanism during regeneration. Thus, for the first time, the results presented here provide direct evidence for the role of polyfucosylated glycan-receptor interactions in the regeneration of H. magnipapillata.

Comparisons of N-glycans across invertebrate phyla

“…It may come as a surprise that even relatively primitive animals have tri- or tetra-antennary N-glycans as found in Hydra, molluscs, insects and nematodes (Eckmair et al , 2016; Kang et al , 1993; Kurz et al , 2015; Kurz et al , 2013; Morelle et al , 2000; Sahadevan et al , 2014). The exact nature of the tri-antennary glycans varies, as GlcNAc-TIV products occur in molluscs and insects (Kurz et al , 2015; Kurz et al , 2013), but GlcNAc-TV acts in glycan biosynthesis in a number of nematodes such as C. elegans and Pristionchus pacificus (Yan et al , 2015c) .…”

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2013–2014

“…On a more conventional level, bi‐ and tri‐antennary glycans with up to twelve, sixteen and twenty‐four fucose residues, respectively have been identified on the galactose and GlcNAc residues of the antennae from Hydra magnipapillata (Sahadevan et al, ) (Fig. ).…”

“…Symbols for the monosaccharide constituents (CFG nomenclature) are shown at the top of the figure. Reprinted with permission from Sahadevan et al (). Copyright 2014 American Chemical Society.…”

Profiling of glycan alterations in regrowing limb tissues of Cynops orientalis

“…Hydra magnipapillata expresses unique polyfucosylated, LacdiNAc antennary N‐ and O ‐glycans. Inhibition of the binding of polyfucosylated glycans with their endogenous lectins using Lotus tetragonolobus agglutinin (LTA) abolishes the regeneration of head and foot . Notch is a ∼300 kDa transmembrane protein of which a large proportion is an extracellular domain containing 36 tandem EGF repeats, many of which are modified with O‐fucose by the enzyme protein O‐fucosyltransferase1 (Pofut1).…”

“…Complex carbohydrates or glycans are known to play important functions in physiology and disease, undoubtedly including during development and regeneration, such as neuronal development, axon regeneration, axon growth and guidance, Hydra regeneration, Xenopus larval tail regeneration, and zebrafish fin and heart regeneration. Even glycosaminoglycans (GAGs) are involved in Xenopus laevis and salamander limb regeneration.…”