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Yuri Gagarin Is Required for Actin, Tubulin and Basal Body Functions in Drosophila Spermatogenesis

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Yuri Gagarin Is Required for Actin, Tubulin and Basal Body Functions in Drosophila Spermatogenesis 1926 Research Article yuri gagarin is required for actin, tubulin and basal body functions in Drosophila spermatogenesis Michael J. Texada, Rebecca A. Simonette, Cassidy B. Johnson, William J. Deery and Kathleen M. Beckingham* Department of Biochemistry and Cell Biology, MS-140, Rice University, 6100 South Main Street, Houston, TX 77005, USA *Author for correspondence (e-mail: [email protected]) Accepted 20 March 2008 Journal of Cell Science 121, 1926-1936 Published by The Company of Biologists 2008 doi:10.1242/jcs.026559 Summary Males of the genus Drosophila produce sperm of remarkable the yuri mutant, late clusters of syncytial nuclei are deformed length. Investigation of giant sperm production in Drosophila and disorganized. The basal bodies are also mispositioned on melanogaster has demonstrated that specialized actin and the nuclei, and the association of a specialized structure, the microtubule structures play key roles. The gene yuri gagarin centriolar adjunct (CA), with the basal body is lost. Some of (yuri) encodes a novel protein previously identified through its these nuclear defects might underlie a further unexpected role in gravitaxis. A male-sterile mutation of yuri has revealed abnormality: sperm nuclei occasionally locate to the wrong ends roles for Yuri in the functions of the actin and tubulin structures of the spermatid cysts. The structure of the axonemes that grow of spermatogenesis. Yuri is a component of the motile actin cones out from the basal bodies is affected in the yuri mutant, that individualize the spermatids and is essential for their suggesting a possible role for the CA in axoneme formation. formation. Furthermore, Yuri is required for actin accumulation in the dense complex, a microtubule-rich structure on the sperm Key words: Drosophila, Spermatogenesis, Actin, Tubulin, Basal nuclei thought to strengthen the nuclei during elongation. In body, Chordotonal organ, Centriole Introduction sperm. The gene is only highly conserved in the genus Drosophila, A unique feature of the genus Drosophila is the formation of suggesting specialized roles in these organisms. Interestingly, yuri unusually long sperm tails. Sperm lengths of millimeters are was initially identified through its function in another specialized common within this group, with the 1.8 mm sperm of D. organ system of insects and arthropods: the chordotonal organs. Journal of Cell Science melanogaster being fairly typical. This marked expansion in sperm These are complex mechanosensory structures with roles in length reflects an unusual aspect of spermatogenesis in these proprioception and graviperception. The first mutation at the locus, organisms: in contrast to other species in which an intraflagellar yuric263, was identified in a screen for mutants affecting gravitaxis. transport system is used for growth of the sperm flagellum (Scholey, Altered gravitaxis was shown to result from perturbed expression 2006), Drosophila sperm axonemes are assembled in syncytial cysts of yuri in subsets of chordotonal neurons (Armstrong et al., 2006). by a mechanism that does not require, and is not limited by, this The molecular functions of the locus identified here suggest that system (Han et al., 2003; Sarpal et al., 2003). This unusual sperm yuri mediates specialized actin- and microtubule-related activities axoneme development and the resulting expansion of sperm tail in Drosophila tissues. length have led to distinctive features of spermatogenesis not found in other species. In D. bifurca, a special ‘sperm roller’ has evolved Results to package its 6-centimeter-long gametes (Joly et al., 2003). In D. The yuri locus in D. melanogaster and other Drosophilids melanogaster, a highly evolved individualization process that In addition to the cDNA (GH14032) encoding a ~30 kDa protein generates 64 individual sperm from an elongate cyst containing 64 that we used previously (Armstrong et al., 2006), we identified 11 syncytial spermatids has been identified and studied (Noguchi and further yuri ESTs/cDNAs from adult testis, ovary, S2 cells and Miller, 2003; Tokuyasu et al., 1972a). The distinctive molecular embryos through FlyBase. Sequencing of these new cDNAs mechanisms needed for this process include a motile filamentous established that three major transcript classes are generated from actin system (the investment, or actin, cones) that traverses the entire yuri (Fig. 1). Two promoters are used, with the medium transcripts length of the sperm tails, removing excess cytoplasm and investing initiated at the proximal promoter and the short and long classes each sperm in its own plasma membrane. A specialized microtubule- from the distal promoter. However, all isoforms begin at one of rich structure (the dense complex) is also associated with the sperm two closely positioned ATGs. The short transcript class encodes nuclei and functions to position the basal body and also possibly the ~30 kDa protein identified previously. The medium class to strengthen the nuclei as they undergo extreme condensation encodes isoforms of 64-65 kDa that extend ~400 amino acids (A. D. Tates, Cytodifferentiation during spermatogenesis in further at the C-terminus. The long class, encoding proteins of 101- Drosophila melanogaster, PhD thesis, Rijksuniversiteit Leiden, The 107 kDa, extends an additional ~300 amino acids C-terminally. Netherlands, 1971) (Tokuyasu, 1974). The short yuri isoform is novel, with only a single recognizable We have identified a locus, yuri gagarin (yuri), that we show motif (a polyproline stretch). However, the two longer forms here has multiple roles in the generation of elongate individualized contain coiled-coil motifs with weak similarity (~20% identity) to yuri gagarin function in spermatogenesis 1927 Fig. 1. Transcripts, proteins and mutations at the Drosophila yuri locus. (A) Two promoters (proximal and distal) generate three classes of yuri transcripts. The two medium transcripts differ by the presence of an intron between exons 1bЈ and 1bЉ. Exon 4, the 5Ј boundary of which is not defined (Materials and Methods), is included in some long transcripts. The original P{GawB} insertion (yuric263) and the DNA deleted in three imprecise excisions (LE1, L5 and F64) are shown. (B) Three Yuri isoform classes arise from the three transcript classes. Structural motifs are indicated. those in many fibrillar proteins that dimerize, such as myosin heavy Ubiquitous expression of the three major Yuri isoforms chain and CLIP-190. The strongest match is to the coiled-coil of To investigate Yuri expression, we generated antibodies against Sticky, the Drosophila citron kinase (Sweeney et al., 2008). the sequences common to all isoforms (see Materials and yuri is unique in the D. melanogaster genome, once the weak Methods). Immunoblots of yuri+ embryos and embryos lacking similarities to coiled-coil regions are disregarded. Thus, to avoid yuri established the specificity of our antisera and their ability to spurious similarities, the shortest yuri isoform was used to find yuri detect the three predicted Yuri isoform classes (Fig. 3A). These orthologs in other organisms. Significant matches were found in blots also demonstrated that only the short Yuri isoform is all 11 sequenced Drosophila genomes (Drosophila 12 Genomes maternally loaded into the embryo, with the longer isoforms Consortium, 2007), but none was identified in other evolutionary appearing later in embryogenesis (Fig. 3A,B). In later stages, all orders or other insects, including the closest Dipteran relatives, the three isoform classes are ubiquitously expressed (Fig. 3C). The Culicidae (mosquitoes) (Fig. 2). Sequence conservation within the ~65 kDa class is most abundant in most situations, although in Drosophila genus was high (91-37% sequence identity, 93-57% testis and thorax the other isoforms are also highly expressed (Fig. similarity) across the entire ~100 kDa isoform of D. melanogaster. 3C). The existence of at least two isoforms for both the ~100 kDa Journal of Cell Science yuri therefore appears to be a Drosophila-specific gene. Most species and ~65 kDa classes was confirmed by these experiments. have one yuri gene, but two related genes are present in D. Additional bands were sometimes present that probably represent pseudoobscura and D. persimilis. specific degradation products, as they were largely missing in Fig. 2. Evolutionary conservation of yuri in Drosophila species. Yuri orthologs are detectable in 12 Drosophila species, but not outside the genus. The ~100 kDa isoform is more conserved than the ~30 kDa isoform. Similarity is computed as the global fraction of residues of the D. melanogaster protein that are present as similar residues in orthologs; these are lower than the local similarity scores from BLAST programs. The GLEANR data set contains consensus sets of predicted proteins for the 12 Drosophila species and was searched using the protein-to-protein BLASTP program. Because protein predictions are not available (NA) for non-Drosophila species, the 30 kDa search was repeated for all sequenced insect species using the protein-to- DNA TBLASTN program. Tree image is from FlyBase (Crosby et al., 2007). 1928 Journal of Cell Science 121 (11) Fig. 3. The distribution of Yuri isoforms throughout development. Immunoblots for Yuri isoforms are shown. (A) Specificity of Yuri antibodies. Lane 1, 30 unfertilized eggs from Df(2L)do1/CyO-GFP mothers [Df(2L)do1 removes yuri]. Lane 2, 30 terminal homozygous Df(2L)do1 embryos. Lane 3, 30 terminal homozygous CyO-GFP (homozygous yuri+) embryos.
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