The Glycosylphosphatidylinositol Anchor: A Linchpin for Cell Surface Versatility of Trypanosomatids

Abstract

The use of glycosylphosphatidylinositol (GPI) to anchor proteins to the cell surface is widespread among eukaryotes. The GPI-anchor is covalently attached to the C-terminus of a protein and mediates the protein’s attachment to the outer leaflet of the lipid bilayer. GPI-anchored proteins have a wide range of functions, including acting as receptors, transporters, and adhesion molecules. In unicellular eukaryotic parasites, abundantly expressed GPI-anchored proteins are major virulence factors, which support infection and survival within distinct host environments. While, for example, the variant surface glycoprotein (VSG) is the major component of the cell surface of the bloodstream form of African trypanosomes, procyclin is the most abundant protein of the procyclic form which is found in the invertebrate host, the tsetse fly vector. Trypanosoma cruzi, on the other hand, expresses a variety of GPI-anchored molecules on their cell surface, such as mucins, that interact with their hosts. The latter is also true for Leishmania, which use GPI anchors to display, amongst others, lipophosphoglycans on their surface. Clearly, GPI-anchoring is a common feature in trypanosomatids and the fact that it has been maintained throughout eukaryote evolution indicates its adaptive value. Here, we explore and discuss GPI anchors as universal evolutionary building blocks that support the great variety of surface molecules of trypanosomatids.

Secretomic Insights into the Pathophysiology of Venturia inaequalis: The Causative Agent of Scab, a Devastating Apple Tree Disease

“…Deeploc, BUSCA, and Cello found 946, 939, and 759 extracellular proteins, respectively, and 664 were common predictions of all three programs. The final secretome of V. inaequalis (647 predicted proteins) was obtained by filtering GPI-anchored proteins (17) that facilitate protein binding to the outer face of the lipid bilayer [ 47 ].…”

Role of a 49 kDa Trypanosoma cruzi Mucin-Associated Surface Protein (MASP49) during the Infection Process and Identification of a Mammalian Cell Surface Receptor

“…Several proteins have been proposed to be involved in the binding–invasion process, but which surface proteins interact specifically with a host-cell receptor is poorly known. The interaction in these regions seems to be mediated in part by GPI-anchored surface proteins [ 37 ].…”

The endoplasmic reticulum of trypanosomatids: An unrevealed road for chemotherapy

“…The most striking illustration of the secretory pathway complexity in Kinetoplastids is the higher prevalence of molecules linked to glycosyl phosphatidylinositol (GPI) on the cell surface compared to the density of transmembrane proteins. In bloodstream form of T. brucei , for instance, the plasma membrane is decorated with 1 x10 7 copies of the variant surface glycoproteins (VSGs) ( Borges et al., 2021 ; de Castro Neto et al., 2021 ). Along contributing with the invasion process, the higher density of this class of molecule precluding immune recognition of less abundant invariant surface determinants.…”

“…T. cruzi is also covered by a thick coat of glycoconjugates, mostly composed by a family of mucin-like glycoprotein ( Acosta-Serrano et al., 2001 ; Borges et al., 2021 ). The carbohydrate in the mucins fulfils crucial functions, the most important of which being the accepting of sialic acid from the host, which is needed for infection ( Giorgi and Lederkremer, 2020 ).…”