Show simple item record

dc.contributor.authorSmith, Michelle Ken_US
dc.contributor.authorWakimoto, Barbara T.en_US
dc.date.accessioned2010-05-06T20:09:07Z
dc.date.available2010-05-06T20:09:07Z
dc.date.issued2007-03-26en_US
dc.identifier.citationSmith M, Wakimoto B. Complex regulation and multiple developmental functions of misfire, the Drosophila melanogaster ferlin gene. BMC Developmental Biology. 2007;7(1):21.en_US
dc.identifier.other10.1186/1471-213X-7-21en_US
dc.identifier.urihttp://www.biomedcentral.com/1471-213X/7/21en_US
dc.identifier.urihttp://hdl.handle.net/1773/15872
dc.description.abstractBackground: Ferlins are membrane proteins with multiple C2 domains and proposed functions in Ca2+ mediated membrane-membrane interactions in animals. Caenorhabditis elegans has two ferlin genes, one of which is required for sperm function. Mammals have several ferlin genes and mutations in the human dysferlin (DYSF) and otoferlin (OTOF) genes result in muscular dystrophy and hearing loss, respectively. Drosophila melanogaster has a single ferlin gene called misfire (mfr). A previous study showed that a mfr mutation caused male sterility because of defects in fertilization. Here we analyze the expression and structure of the mfr gene and the consequences of multiple mutations to better understand the developmental function of ferlins. Results: We show that mfr is expressed in the testis and ovaries of adult flies, has tissue-specific promoters, and expresses alternatively spliced transcripts that are predicted to encode distinct protein isoforms. Studies of 11 male sterile mutations indicate that a predicted Mfr testis isoform with five C2 domains and a transmembrane (TM) domain is required for sperm plasma membrane breakdown (PMBD) and completion of sperm activation during fertilization. We demonstrate that Mfr is not required for localization of Sneaky, another membrane protein necessary for PMBD. The mfr mutations vary in their effects in females, with a subset disrupting egg patterning and causing a maternal effect delay in early embryonic development. Locations of these mutations indicate that a short Mfr protein isoform carries out ferlin activities during oogenesis. Conclusion: The mfr gene exhibits complex transcriptional and post-transcriptional regulation and functions in three developmental processes: sperm activation, egg patterning, and early embryogenesis. These functions are in part due to the production of protein isoforms that vary in the number of C2 domains. These findings help establish D. melanogaster as model system for understanding ferlin function and dysfunction in animals, including humans.en_US
dc.description.sponsorshipNSRA Grant T32 HD007183-26 from the NIH-NICHD to M.K.S., and by National Science Foundation grant DCB0211733 and Washington Research Foundation Professorship of Basic Biological Sciences to B.T.W.en_US
dc.language.isoen_USen_US
dc.titleComplex regulation and multiple developmental functions of misfire, the Drosophila melanogaster ferlin geneen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record