遺傳分析ina-1與cM9	在線蟲細胞凋亡的角色

細胞計畫性的死亡是多細胞生物發生過程中的正常程序用來消滅不需要的細胞；而細胞吞噬則是必須的程序用以清除因細胞自我死亡所產生的細胞屍體。今年來的研究證明這些訊息傳遞路徑在物種間是有保守性的。Integrins 是一個很大的家族由異分子組成的細胞表面受器，參與細胞黏合、細胞遷移與細胞訊息傳遞過程。ina-1是線蟲integrin 的α次分子，主要影響神經及DTC細胞的遷移。我們發現當ina-1 缺失時，會導致線蟲細胞屍體數目增多，且我們證明此一增多的情況不是因為integrin 缺失導致細胞有anoikis 的性狀，並且這些細胞屍體都是由正常的細胞死亡產生的。這些結果顯示ina-1突變所產生的細胞屍體增加可能為影響了細胞吞噬的過程。我們進一步的去尋找ina-1與其他已知參與在細胞吞噬作用的其他成員之間的關係，發現ina-1可能可以定義一個新的細胞吞噬訊息傳遞路徑。 M9是人類肌肉相關蛋白。我們發現當cM9（線蟲的M9同源基因）突變時，在胚胎發育過程會產生比較少的細胞屍體。並且cM9突變種在腹節神經細胞裡有多餘的細胞逃過細胞死亡的命運而存活下來。因此，我們認為cM9應該為促進細胞死亡的基因。除此之外，我們在觸覺神經中過量表現ced-3(caspase)的情況下過量表現cM9，發現比起單獨ced-3所引發的觸覺神經細胞死亡，在ced-3和cM9一起過量表現有更多的神經細胞死亡。此一結果暗示cM9引發的細胞死亡可能是caspase independent。

關鍵字

線蟲；細胞凋亡

並列摘要

During the development of multicellular organisms, programmed cell death (apoptosis) is a normally occurring process used to eliminate unnecessary cells. Engulfment is an essential process for clearance of cell corpse generated by apoptosis. Recent studies demonstrate that the molecular control of these processes is evolutionally conserved in metazoans. Integrins are a large family of heterodimeric cell surface receptors involved in cell adhesion, cell migration and signal transduction. INA-1 is C. elegans integrin α subunit that plays roles in neural development and DTC migration. We found that ina-1 mutations increased number of cell corpses in embryos and that this ina-1-mediated enhancement in cell-corpse number is through programmed cell death. This implies that ina-1 might be important in the engulfment process to remove cell corpses. Interestingly, ina-1 acts synergistically with previously identified engulfment genes, suggesting that ina-1 may act in parallel to these genes during programmed cell death and may define a new engulfment pathway in C. elegans. M9 is human muscle specific protein. We found that animals bear a mutation in cM9 (which is C. elegans homolog of M9) decreased numbers of cell corpses throughout embryogenesis. We further showed that cM9 mutant animals had extra surviving cells in the ventral cord in the engulfment-defective ced-2 mutant background. Together these data suggested that cM9 function as a positive mediator during apoptosis in C. elegans. We also showed that cM9 acts synergistically with ced-3 (which is a caspase) to promote cell-killing, suggesting that cM9 may mediate apoptosis through a ced-3 independent pathway.

並列關鍵字

C. elegans ； apoptosis ； engulfment

參考文獻

Albert M. et al. (2000) αvβ5 integrin recruits the CrkII–Dock180–Rac1 complex for phagocytosis of apoptotic cells. Nat. Cell Biol. 2:899–905.

Baum P.D. and Garriga G. (1997) Neuronal migrations and axon fasciculation are disrupted in ina-1 integrin mutants. Neuron 19:51-62.

Brown N.H. (2000) Cell-cell adhesion via the ECM: integrin genetics in fly and worm. Matrix Biol. 19:191–201

Conradt B. (2002) With a little help from your friends: cells don't die alone. Nat Cell Biol. 4:E139-43.

Conradt B., and Horvitz H.R. (1998) The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell 93:519-29.

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遺傳分析ina-1與cM9 在線蟲細胞凋亡的角色

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