MOLECULAR-CLONING AND CHARACTERIZATION OF AN INVERTEBRATE CELLULAR RETINOIC ACID-BINDING PROTEIN

We have cloned a cDNA and gene from the tobacco hornworm, Manduca sext a, which is related to the vertebrate cellular retinoic acid binding p roteins (CRABPs). CRABPs are members of the superfamily of lipid bindi ng proteins (LBPs) and are thought to mediate the effects of retinoic acid (RA) on morphogenesis, differentiation, and homeostasis. This dis covery of a Manduca sexta CRABP (msCRABP) demonstrates the presence of a CRABP in invertebrates. Compared with bovine/murine CRABP I, the de duced amino acid sequence of msCRABP is 71% homologous overall and 88% homologous for the ligand binding pocket, The genomic organization of msCRABP is conserved with other CRABP family members and the larger L BP superfamily. Importantly, the promoter region contains a motif that resembles an RA response element characteristic of the promoter regio n of most CRABPs analyzed. Three-dimensional molecular modeling based on postulated structural homology with bovine/murine CRABP I shows msC RABP has a ligand binding pocket that can accommodate Rk The existence of an invertebrate CRABP has significant evolutionary implications, s uggesting CRABPs appeared during the evolution of the LBP superfamily well before vertebrate/invertebrate divergence, instead of much later in evolution in selected vertebrates.