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Review
. 2008 Apr 1;103(5):1327-43.
doi: 10.1002/jcb.21513.

Secretion without Golgi

Igor Prudovsky  1 , Francesca Tarantini, Matteo Landriscina, David Neivandt, Raffaella Soldi, Aleksandr Kirov, Deena Small, Karuppanan Muthusamy Kathir, Dakshinamurthy Rajalingam, Thallapuranam Krishnaswamy Suresh Kumar
Affiliations
Review

Secretion without Golgi

Igor Prudovsky et al. J Cell Biochem. .

Abstract

A growing number of proteins devoid of signal peptides have been demonstrated to be released through the non-classical pathways independent of endoplasmic reticulum and Golgi. Among them are two potent proangiogenic cytokines FGF1 and IL1alpha. Stress-induced transmembrane translocation of these proteins requires the assembly of copper-dependent multiprotein release complexes. It involves the interaction of exported proteins with the acidic phospholipids of the inner leaflet of the cell membrane and membrane destabilization. Not only stress, but also thrombin treatment and inhibition of Notch signaling stimulate the export of FGF1. Non-classical release of FGF1 and IL1alpha presents a promising target for treatment of cardiovascular, oncologic, and inflammatory disorders.

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Figures

Fig. 1
Fig. 1
Current working model of stress-induced FGF1 release. Stress enhances the expression of S100A13 and induces the actin cytoskeleton-dependent translocation of FGF1, S100A13, and p40 Syt1 to the inner leaflet of the cell membrane where they bind to acidic phospholipids. SK1 located on the inner leaflet of the cell membrane serves as a source of copper ions (which are provided to SK1 by the transmembrane copper transporters). Copper delivered by SK1 is required for the formation of the release complex. This complex includes the covalent FGF1 dimer, non-covalent S100A13 dimer, p40 Syt1 and SK1. The release complex binds to Anx II, which is also located on the inner leaflet of the cell membrane. Transmembrane flipping of acidic phospholipids results in the export of the FGF1 release complex and Anx II.
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