9.A.71 The Glycosylphosphatidylinositol-anchored Protein (GPI-AP) Family 

The exposure of phosphatidylserine (PS) on the cell surface is a general marker of apoptotic cells. Non-apoptotic PS externalization is induced by several activation stimuli, including engagement of immunoreceptors. Immune cells can also be activated by aggregation of glycosylphosphatidylinositol-anchored proteins (GPI-APs). These proteins lack transmembrane and cytoplasmic domains, but mediate PS externalization. Smrz et al. 2007 showed that GPI-APs in rodent mast cells induce a rapid and reversible externalization of PS by a non-apoptotic mechanism. PS externalization triggered by GPI-AP-specific monoclonal antibodies was dependent on the activity of H+-ATP synthase and several other enzymes involved in mast cell signaling. Disruption of actin cytoskeleton by latrunculin B or of plasma membrane integrity by methyl-beta-cyclodextrin had opposite effects on PS externalization triggered through GPI-AP or the high affinity IgE receptor. PS externalization mediated by GPI-APs was also observed in some other cells, and its extent varied with antibodies used. Effects of different antibodies on PS externalization were additive, indicating that independent stimuli converge onto a signaling pathways leading to PS externalization. This mechanism could contribute to 'inside-out' signaling in response to pathogens and other external activators and/or to initiation of other functions associated with PS externalization. These proteins may be distantly related to those in TC family 8.A.31.

The reaction catalyzed by GPI-AP is:

PS (in) ⇌ PS (out)

This family belongs to the .



Smrz, D., L. Dráberová, and P. Dráber. (2007). Non-apoptotic phosphatidylserine externalization induced by engagement of glycosylphosphatidylinositol-anchored proteins. J. Biol. Chem. 282: 10487-10497.


TC#NameOrganismal TypeExample

Glycosylphosphatidylinositol-anchored protein (GPI-AP) of 158 aas. Plays a role in the apoptotic pathway by mediating reversible phosphatidyl serine export (Smrz et al. 2007).  May have N- and C-terminal TMSs.

GPI-AP of Homo sapiens