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Updated: May 31, 2025

Construction of Model Lipid Membranes Incorporating G-protein Coupled Receptors GPCRs
Published on: February 5, 2022
Unlocking the signaling potential of GPI-anchored proteins through lipolytic cleavage
Razvan Borza1, Elisa Matas-Rico2, Anastassis Perrakis1
1Division of Biochemistry, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Abstract:
Glycosylphosphatidylinositol (GPI)-anchored proteins (APs) regulate numerous biological processes through interaction with signaling effectors at the cell surface. As a unique feature, GPI-APs can be released from their anchors by multi-pass GPI-specific phospholipases (types A2, C, and D) to impact signaling networks, phenotype, and cell fate; however, many questions remain outstanding. Here, we discuss and expand our current understanding of the distinct GPI-specific phospholipases, their substrates, effector pathways, and emerging physiological roles, with a focus on the six-transmembrane ecto-phospholipases GDE2 (GDPD5) and GDE3 (GDPD2). We provide structural insight into their AlphaFold-predicted inner workings, revealing how transmembrane (TM) domain plasticity may enable GPI-anchor binding and hydrolysis. Understanding lipolytic cleavage of GPI-APs adds a new dimension to their signaling capabilities and biological functions.
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