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Review
. 2012 Aug;1821(8):1089-95.
doi: 10.1016/j.bbalip.2012.01.003. Epub 2012 Jan 14.

Connecting vesicular transport with lipid synthesis: FAPP2

Giovanni D'Angelo  1 , Laura Rita Rega, Maria Antonietta De Matteis
Affiliations
Review

Connecting vesicular transport with lipid synthesis: FAPP2

Giovanni D'Angelo et al. Biochim Biophys Acta. 2012 Aug.

Abstract

Next to the protein-based machineries composed of small G-proteins, coat complexes, SNAREs and tethering factors, the lipid-based machineries are emerging as important players in membrane trafficking. As a component of these machineries, lipid transfer proteins have recently attracted the attention of cell biologists for their involvement in trafficking along different segments of the secretory pathway. Among these, the four-phosphate adaptor protein 2 (FAPP2) was discovered as a protein that localizes dynamically with the trans-Golgi network and regulates the transport of proteins from the Golgi complex to the cell surface. Later studies have highlighted a role for FAPP2 as lipid transfer protein involved in glycosphingolipid metabolism at the Golgi complex. Here we discuss the available evidence on the function of FAPP2 in both membrane trafficking and lipid metabolism and propose a mechanism of action of FAPP2 that integrates its activities in membrane trafficking and in lipid transfer. This article is part of a Special Issue entitled Lipids and Vesicular Transport.

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Figures

Fig. 1
Fig. 1
Protein sequence alignment of the FAPP2 protein in different organisms. Strongly and moderately conserved residues are shown in red and blue, respectively. Protein regions corresponding to the PH and GLTPH domains are indicated.
Fig. 2
Fig. 2
The lipid binding domains of FAPP2: the PH domain and the GLTPH domain. a) The FAPP2 PH domain. Upper panel: sequence alignment of the FAPP2 PH domain in different species. Bars on top of the sequence indicate residues involved in PtdIns4P binding (blue bars), ARF1 binding (green bars) or in the formation of the hydrophobic hairpin loop (red bars). Lower panel: homology modelling of the FAPP2-PH structure derived from the FAPP1-PH crystal structure (PDB ID: 3RCP) using Swiss-model highlighting, on the left, the conservation of the different regions (strongly and moderately conserved regions coloured in red and blue, respectively) and on the right the regions involved in PtdIns4P binding (blue), ARF1 binding (green) or in the formation of the hydrophobic hairpin loop (red). b) The FAPP2 GLTPH domain. Upper panel: sequence alignment of the FAPP2 GLTPH domain in different species. Bars on top of the sequence indicate residues involved in glycolipid binding. Lower panel: homology modelling of the FAPP2-GLTPH structure derived from the GLTP crystal structure (PDB ID: 1SWX) using Swiss-model , highlighting, on the left, the conservation of the different regions (strongly and moderately conserved regions coloured in red and blue, respectively) and, on the right, the residues involved in glycolipid binding (cyan).
Fig. 3
Fig. 3
The roles of FAPP2 in the biogenesis of transport carriers at the TGN. a) FAPP2 might contribute to sort specific cargoes within specific membrane microdomains by fostering the synthesis of GSLs that segregate from other membrane lipids thus forming sorting platforms. b) FAPP2 is involved in the budding of post-Golgi carrier by inducing membrane bending through the insertion of the hydrophobic loop (located in its PH domain) into the lipid bilayer. c) The combined sorting and budding activities of FAPP2 can coordinate the formation of specific post-Golgi carriers (most probably apically directed) with specific lipid and protein composition.
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References

    1. Rothman J.E. Mechanisms of intracellular protein transport. Nature. 1994;372:55–63. - PubMed
    1. Segev N. Coordination of intracellular transport steps by GTPases. Semin. Cell Dev. Biol. 2010;22:33–38. - PMC - PubMed
    1. Field M.C., Sali A., Rout M.P. Evolution: On a bender — BARs, ESCRTs, COPs, and finally getting your coat. J. Cell Biol. 2011;193:963–972. - PMC - PubMed
    1. Waters M.G., Pfeffer S.R. Membrane tethering in intracellular transport. Curr. Opin. Cell Biol. 1999;11:453–459. - PubMed
    1. Malsam J., Kreye S., Sollner T.H. Membrane fusion: SNAREs and regulation. Cell. Mol. Life Sci. 2008;65:2814–2832. - PMC - PubMed

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