Function of zona pellucida domain proteins
The first specific interaction between sperm and egg occurs at an extracellular matrix (ECM) called the zona pellucida (zp). The zp does not only provide specific receptors for incoming sperm, but has other important functions. It can induce the acrosome reaction on the sperm head, and by reacting to the release of cortical granules from the oocyte, provides the major block to polyspermy. It also serves as a protection for the fertilized egg and early mammalian embryo during its travel to the point of implantation. The zp then has to break open in a tightly controlled timed program to allow the embryo to hatch and contact the maternal endometrium.
Studies in mice have shown that the zp consists of only 3 glycoproteins which all share a 260 amino acid domain called the zp domain. These proteins are coordinately expressed by the oocyte at the transition from the primordial to the primary stage. In other animals, however, they are often expressed by somatic tissues. In birds, we have shown that the two main components of the zp, ZP1 and ZPC, are made by the liver and granulosa cells, respectively. Similar extraoocytic expression of zp proteins is now established in many animals including mammals. In these cases, the proteins have to travel to their final destination and then polymerize to form the growing zp. A major aim of this project is to investigate how these factors are targeted to the site of zp assembly. We have shown that purified native ZPC will self-assemble to larger structures if its concentration is sufficiently high and focus our attention on optimal conditions for assembly of the zp in vitro. Special interest is being paid to the role of follicle-derived factors like GDF9, BMP15, activin, perlecan, etc. in this process.
In addition, the number of ovarian zp proteins besides the three canonical zp components is steadily increasing. Thus, in birds, we have up to now identified 8 follicular zp proteins. The function of these factors is entirely unknown. Another aim of this project is to delineate the roles these proteins play during the lifecycle of the ovary and in different organs. We have already shown that one of the liver-derived zp proteins, ZPAY, is not targeted to the ovary, but is associated in the brain and the kidney with cells lining tubular structures, such as cerebral smooth muscle cells, and the proximal tubulus, respectively.