The structure and function of molecules which regulate the cell membrane phospholipid bi-layer.

点击翻译按钮获取中文摘要

Plasma membrane has an asymmetric lipid distribution. Whereas both plasma membrane leaflets are mainly composed of choline-containing phospholipids (phosphatidylcholine and sphingomyelin), the inner leaflet is enriched relative to the outer leaflet in primary amine-containing phospholipids (phosphatidylserine (PS), and phosphatidylethanolamine). Disruption of this normal lipid distribution is an important element in blood platelet activation and in apoptosis. Loss of lipid asymmetry with concomitant PS exposure at the surface of activated platelets promotes assembly of active enzyme-substrate complexes of the blood coagulation cascade. The PS exposure on apoptotic cells triggers recognition and clearance by phagocytes. Phospholipid scramblase 1 (PLSCR1) has been proposed to catalyze both inward and outward transbilayer lipid movement in response to elevated cytoplasmic Ca^<2+>, and it may contribute to cell surface PS exposure during platelet activation and early stages of apoptosis. We have identified 5 alternatively spliced scrambrase transcripts by PCR of human fetal kidney cDNA library, using oligonucleotide primers to regions containing the start and stop codons of phospholipid scramblase 1 (PLSCR1). In all variants of PLSCR1 mRNA (PLSCR1 mRNA was designated Scrla), the exon 4 of Scrla is spliced out, resulting in a frame shift in the exon 5 coding sequence, generating a premature stop codon in the exon 5. While the full-length Scrla encodes for a protein of 318 amino acids (PLSCR1α), all variants encode a protein of 41 amino acids (PLSCR1β). A novel carboxyl-terminal (C-terminal) tail of 10 amino acids does not show any homology to sequences in the protein database. PLSCR1β contains Pro-X-X-Pro and Pro-Pro-X-Tyr motifs, which may serve as potential binding sites for proteins containing SH3 and WW domains, respectively. PLSCR1β may interact with an adapter or signaling molecule via these motifs, thus possiblly regulating PLSCR1α function.