Hepatic synthesis, maturation and complex formation between retinol-binding protein and transthyretin.
The retinol/retinol-binding protein/transthyretin complex, that carries and delivers hydrophobic retinol molecules to target cells, is assembled in the hepatocyte endoplasmic reticulum. In this paper, we review data related to events that lead to the formation of this complex, including transthyretin oligomerization and retinol-binding protein secretion. Our studies on transthyretin oligomerization have demonstrated that cleavage of signal peptide and the environment of endoplasmic reticulum influence transthyretin oligomerization. In vitro, mutated transthyretin without signal sequence fails to form dimers, while wild-type transthyretin is translocated into the microsomes where it forms dimers and small amounts of tetramers. In vivo, tetramers were detected in HepG2 cells but not in transfected Cos cells, suggesting that tissue-specific factors affect tetramer stability. In vitamin A deficiency, retinol-binding protein secretion is blocked and the protein accumulates in the endoplasmic reticulum, from where it is promptly released after retinol repletion. We use MMH cells to identify factors involved in complex formation, retention and secretion, the crucial steps to understand the molecular mechanisms underlying vitamin A homeostasis. In parallel, studies on vitamin A transport in fish are in progress; retinol-binding protein and transthyretin have already been characterized in different fish species.
Gaetani
Sancia
S
Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione, Roma, Italy. gaetani@inran.it
Bellovino
Diana
D
Apreda
Marianna
M
Devirgiliis
Chiara
C
D000595:Amino Acid Sequence; D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D011228:Prealbumin / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D011485:Protein Binding; D012177:Retinol-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment
D011228:Prealbumin; D012177:Retinol-Binding Proteins