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Báo cáo khoa học: Secretion of the mammalian Sec14p-like phosphoinositide-binding p45 protein

Protein–lipid interactions are important for protein targeting, signal trans-duction, lipid transport, and the maintenance of cellular compartments and membranes. Specific lipid-binding protein domains, such as PH, FYVE, PX, PHD, C2 and SEC14 homology domains, mediate interactions between proteins and specific phospholipids. | ềFEBS Journal Secretion of the mammalian Sec14p-like phosphoinositide-binding p45 protein Maria Merkulova1 Huong Huynh2 Vitaly Radchenko1 Kan Saito2 Valery Lipkin1 Tatiana Shuvaeva1 and Tomas Mustelin2 1 Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences Moscow Russia 2 Program of Inflammation Infectious and Inflammatory Disease Center and Program of SignalTransduction Cancer Center The Burnham Institute La Jolla CA USA Keywords CRAL TRIO domain GOLD domain nonclassical protein secretion phosphoinositides Sec14p Correspondence T. Mustelin Program of SignalTransduction The Burnham Institute 10901 N. Torrey Pines Road La Jolla CA 92037 USA Fax 1 858 713-6274 Tel 1 858 713-6270 E-mail tmustelin@burnham.org Received 11 March 2005 revised 23 August 2005 accepted 2 September 2005 doi 10.1111 j.1742-4658.2005.04955.x Protein-lipid interactions are important for protein targeting signal transduction lipid transport and the maintenance of cellular compartments and membranes. Specific lipid-binding protein domains such as PH FYVE PX PHD C2 and SEC14 homology domains mediate interactions between proteins and specific phospholipids. We recently cloned a 45-kDa protein from rat olfactory epithelium which is homologous to the yeast Sec14p phosphatidylinositol PtdIns transfer protein and we report here that this protein binds to PtdIns 3 4 5 P3 and far weaker to less phosphorylated derivatives of PtdIns. Expression of the p45 protein in COS-1 cells resulted in accumulation of the protein in secretory vesicles and in the extracellular space. The secreted material contained PtdIns 3 4 5 P3. Our findings are the first report of a Sec14p-like protein involved in transport out of a cell and to the best of our knowledge inositol-containing phospholipids have not previously been detected in the extracellular space. Our findings suggest that p45 and phosphoinositides may participate in the formation of the protective mucus on nasal epithelium. .