The low-density lipoprotein receptor-related protein 2 (LRP2) belongs to the LDL receptor family, a group of closely related and highly conserved type I, endocytic, cell-surface receptors. These ancient proteins share classical structural motives and features, and are involved in an abundance of physiological processes. LRP2, the largest and most promiscuous gene family member, is highly expressed at the apical surface of absorptive epithelia, in tissues and organs including kidney, small intestine, lung, and reproductive tracts.
Its multiple ligands belong to various classes of proteins such as lipoproteins, vitamins, hormones, enzymes, and carrier proteins, which are engaged in distinct cellular pathways and highly diverse biological functions. New roles for LRP2 in vitamin homeostasis, hormone function, and cell signaling have emerged, which have to be elucidated further.
LRP2 has been identified as a key mediator of embryonic nutrition, being highly expressed in the endocytically active yolk sac. To date, LRP2 has been characterized in different species, but the molecular delineation of a homologue in avian species has not been accomplished yet. In order to gain new insights into the biology of this complex protein and to study the regulation of the receptor, we have chosen the chicken, Gallus gallus, as a well-established model organism for studies on lipid metabolism and sex-specific aspects of reproduction.
This thesis not only provides insights in the biology of the avian LRP2 homolog, but also reveals possibly general mechanisms for the hormonal regulation of LRP2.