GPI-specific phospholipase D

Fig. 2. Enzymatic and chemical cleavage sites of GPI anchors useful in identifying GPI anchored membrane proteins. GPI-PLC, GPI-specific phospholipase C GPI-PLD, GPI-specific phospholipase D HF, hydrogen fluoride MONO, nitrous acid NaOH (NH3), mild alkali treatment PI-PLC, phosphatidylinositol-specific phospholipase C. (Redrawn from ref. [178].)...

A GPl-anchor may also allow a protein to be selectively released from the cell surface upon hydrolysis by a GPI-specific phospholipase (e.g., Pl-phospholipase C or GPl-phospholipase D). This has been shown to occur for certain GPI-anchored proteins in mammalian cell culture. One example is GPI-anchored membrane dipeptidase which is released from the adipocyte cell surface by a phospholipase C in response to insulin (S. Movahedi, 2000). Interestingly, other GPI-anchored proteins are not released, indicating a level of regulation in insulin-stimulated hydrolysis of GPI-anchored proteins. GPI-anchored molecules have also been shown to transfer between cells and stably insert in the external leaflet of the acceptor cell s plasma membrane (M.G. Low, 1998). The biological significance of this event is unclear however, the ability of GPI-anchored proteins to transfer between cells has implications for the expression of foreign proteins on the cell surface. 

Glycosylphosphatidylinositol (GPI) anchors are found in many cell surface proteins in eukaryotes, which tether them to the extracellular side of the plasma membrane. The GPI anchor is attached to the C-terminus of a protein via a phosphoetha-nolamine linkage. GPIs and GPI-anchored proteins are built up in the ER and then the modified proteins transit to the cell surface. This posttranslational glyco-lipid modification is mediated by the GPI transamidase (GPI-T) in the ER lumen. The GPI anchor can be hydrolysed by phosphatidylinositol-specific phospholipase C or D (PLC or PLD) which releases the protein moiety into the extracellular milieu... 

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