Live imaging of neuronal degradation by microglia reveals a role for v0-ATPase a1 in phagosomal fusion in vivo (Cell, 2008, 133:916-927)

報告日期: 2009/01/06
報告時間: 15:10/16:00
報告學生: 高增婷
講評老師: 張南山

Living imaging of neuronal degradation by microglia reveals a role for v0-ATPase a1 in phagosomal fusion in vivo
Francesca Peri and Christiane Nüsslein-Volhard
Cell 2008; 133:916-927

Student: 高增婷
Commentator: 張南山 老師
Place: Room 602
Time: 15:10~16:00

   Microglia, the immune cells in central nerve system (CNS), plays a vital role in prevention of microorganism infection and removal of neuronal degraded products.  The apoptosis of neurons is an important process for brain development and function. It had been documented that microglia could remove the degraded neurons through phagocytosis followed digesting neurons by the formation of phagolysosomes. The accumulation and diffusion of these degraded apoptotic materials might be associated with the pathogenic process of neuronal degenerative diseases by damaging the brain tissue. v-ATPases which are the major proton pumps in the membrane are function as the acidification in phagosomal maturation and the a1 subunit of v0-ATPase is involved in the fusion of phagosome and lysosome. In this paper, the authors used zebrafish as a model in vivo to explore the neuronal degradation by microglia and to characterize the role of v0-ATPase al in vesicular fusion. They used Apo-E-GFP transgenic fish to recapitulate the expression pattern to in vivo microglia (Apo-E was a marker of zebrafish microglia). Comparison with v0-ATPa1 knock-down microglia in Apo-E transgenic fish with wild type by specific dye staining (Acridine orange for apoptosis, Lyso Tacker for acidic organelles, and MR Cathepsin, DQ-BSA for lysosome), they demonstrated that the loss of function of v0-ATP al defected the vesicular fusion caused to a large size phagosome with lots of vesicles accumulation. However, the depletion of v0-ATPase al was not affected the acidification of phagosome. It was showed that the knock-down microglia defected in digest the neurons were attributed to the problem in vesicular fusion not in its acidification. Furthermore, a real-time in vivo observation of microglia phagocytosis provided the stronger direct information of molecules and cells interaction. These results might promote the advanced application in understanding the microglia-associated neuronal degenerative diseases.

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