| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
In a preceding international cooperative project, we reported biochemical interaction and possible functional interaction between mammalian septin complexes and the Cdc42 effector protein family, borgs (Nat.Cell Biol., 2001), however, the cellular functions of borgs have been unknown. To study whether the Cdc42-borg signaling system is involved in physiological regulation of the assembly and disassembly of septins, we raised antibody against a major borg species, revealed subcellular localization of the native borg protein, and depleted it by RNAi up to 90%. Unexpectedly, however, the depletion did not affect the localization and assembly of the septins and the major cytoskeleton (unpublished). To explore unidentified molecules that play major roles in the regulation of assembly and disassembly of the septin system, we purified septin-interacting molecules from cell extract and identified several septin-binders by a peptide mass fingerprinting method. We have revealed that a molecule i
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nvolved in an important signal transduction pathway interact with septins both physically and functionally. We are currently testing the relevance of this interaction in tissue culture cells.
In parallel with the above in vitro experiments, we attempted to reveal septin functions in vivo by creating mice lacking a septin gene. Through an unexpected phenotype of absolute male infertility of the septin-knockout mice, we found that a ring-shaped higher-order septin assembly in sperm flagellum (previously known as annulus) is essential for the structural and mechanical integrity of the spermatozoa. Using clinical materials collected under informed consent by urologists specialized in reproductive medicine, we found the ring-shaped higher-order septin assembly is lost in 25% of human asthenospemia, a male infertility syndrome with impaired flagellar motility (Dev.Cell 2005).
Based on the above results, the researcher was invited as an author to review the progress of the septin biology (Curr.Opin.Cell Biol., 2006). Less
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