FARINELLI: ein testisspezifisches VAP-Protein und seine Funktion in der Drosophila-Spermatogenese

This study focuses on the analysis of a novel gene, farinelli (fan), that is required for male fertility in Drosophila. Even though mRNA and protein are already detected in premeiotic stages, spermatogenesis in fan-mutant males is affected during the final differentiation of the postmeiotic germ cells. In spermatogenesis of Drosophila melanogaster a gonial founder cell gives rise to 64 haploid spermatids which are enclosed by a pair of somatically derived cyst cells. Within this cyst the 64 spermatids simultaneously differentiate into motile sperm by complex morphological changes including chromatin condensation and the formation of a flagellum. At the end of the process each spermatozoon becomes surrounded by a complete plasma membrane, the cyst cells are removed and the individual germ cells are released into the seminal vesicle. The loss of the farinelli function invariably causes the degeneration of spermatid bundles before individualization has been completed. It was shown that the condensation of the nucleus as well as the assembly of the protein machinery (investment cone) which triggers the individualization process are disturbed. The fan gene encodes a 24,6 kD integral membrane protein that is exclusively expressed in the male germ cells. The FAN protein shows more than 40% sequence similarity with VAP-related proteins of human and rat. VAP (vesicle associated membrane protein-associated protein) is thought to function in protein transport through the endoplasmic reticulum (ER) and retrograde transport from pre-Golgi intermediates to the ER. In accordance with these data FAN was found to be localized in the ER compartment and, therefore could play an essential role in the transport of proteins involved in the differentiation process.