MOLECULAR CHARACTERISTICS OF INSECT VITELLOGENINS AND VITELLOGENIN RECEPTORS

The recent cloning and sequencing of several insect vitellogenins (Vg) , the major yolk protein precursor of most oviparous animals, and the mosquito Vg receptor (VgR) has brought the study of insect vitellogene sis to a new plane. Insect Vgs ale homologous to nematode and vertebra te Vgs. All but one of the insect Vgs for which we know the primary st ructure are cleaved into two subunits at a site [(R/K)X(R/K)R or RXXR with an adjacent p-turn] recognized by subtilisin-like proprotein conv ertases. In four of the Vgs, the cleavage site is near the N-terminus, but in one insect species, it is near the C-terminus of the Vg precur sor. Multiple alignments of these Vg sequences indicate that the varia tion in cleavage location has not arisen through exon shuffling, but t hrough local modifications of the amino acid sequences. A wasp Vg prec ursor is not cleaved, apparently because the sequence at the presumed ancestral cleavage site has been mutated from RXRR to LYRR and is no l onger recognized by convertases. Some insect Vgs contain polyserine do mains which are reminiscent of, but not homologous to, the phosvitin d omain in vertebrate Vgs. The sequence of the mosquito VgR revealed tha t it is a member of the low-density lipoprotein receptor (LDLR) family . Though resembling chicken and frog VgRs, which are also members of t he LDLR family, it is twice as big, carrying two clusters of cysteine- rich complement-type (Class A) repeats (implicated in ligand-binding) instead of one like vertebrate VgRs and LDLRs. It is very similar in s equence and domain arrangement to the Drosophila yolk protein receptor (YPR), despite a non-vitellogenin ligand for the latter. Though verte brate VgRs, insect VgR/YPRs, and LDLR-related proteins/megalins all ac commodate one cluster of eight Class A repeats, fingerprint analysis o f the repeats in these clusters indicate they are not directly homolog ous with one another, but have undergone differing histories of duplic ations, deletions, and exon shuffling so that their apparent similarit y is superficial. The so-called epidermal growth factor precursor regi on contains two types of motifs (cysteine-rich Class B repeats and YWX D repeats) which occur independently of one another in diverse protein s, and are often involved in protein-protein interactions, suggesting that they potentially are involved in dimerization of VgRs and other L DLR-family proteins. Like the LDLR, but unlike vertebrate VgRs and the Drosophila YPR, the mosquito VgR contains a putative O-linked sugar r egion on the extra-cellular side of the transmembrane domain. Its func tion is unclear, but may protect the receptor from membrane-bound prot eases. The cytoplasmic tail of insect VgR/YPRs contains a di-leucine ( or leucine-isoleucine) internalization signal, unlike the tight-turn t yrosine motif of other LDLR-family proteins. The importance of underst anding the details of yolk protein uptake by oocytes lies in its poten tial for exploitation in novel insect control strategies, and the mole cular characterization of the proteins involved has made the developme nt of such strategies a realistic possibility. (C) 1998 Elsevier Scien ce Ltd. All rights reserved.