File:Vesicle traffic and phagophore.png
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English: Summary of key gene expression changes to ER and Golgi function, vesicular transport, mTOR signalling and autophagy.
The downregulation of multiple transcripts encoding ribosomal proteins, translation initiation factors (eIFs) and the ribosomal subunit, RPS6 suggests a global repression of translation within the cell (1). SEC23 and SEC24 coat vesicles into which immature proteins are packaged and are upregulated. Vesicles are transported along microtubules (MTs) from the ER-Golgi intermediate compartment; however, downregulation of the main components of microtubules, TUBA and TUBB, and the MT-stabilising proteins, MAP1S and MAP4, indicates MT disassembly and therefore disruption to vesicular transport (2). This is enhanced by upregulation of STMN1, a MT-destabilising protein, whose over-expression has also been demonstrated to result in Golgi fragmentation. Downregulation of transcripts maintaining Golgi structure (GLG1, GORASP1, COG2 and COG7) support the hypothesis of Golgi fragmentation (3). COPI is used to coat empty vesicles exiting the Golgi for recycling back to the ER, however, two main constituents, COPE and COPZ1, are downregulated, as is USE1, which is required for vesicle fusion with the ER. These findings predict an eventual deficit of material available to ER for the packaging of newly synthesised proteins (4). There is dysregulation of multiple SNARE transcripts, which are required for vesicle fusion. BOS1 and SEC22 are upregulated, which may be the Golgi's response to the reduction in vesicles being transported along destabilised microtubules. Multiple SNAREs and adaptor proteins (VTI1, STX4, AP1B1, AP2A2, AP2S1, AP3D1 and AP4B1), which are required for fusion between vesicles carrying mature proteins and the cell surface, endosomes and lysosomes, are downregulated, predicting impairment in the delivery of proteins throughout the cell (5). Finally, inhibition of autophagy by the mTORC1 complex and downregulation of ATG1, which forms the phagophore assembly site (PAS) with ATG17 and ATG13 to initiate autophagy, indicates a decrease in the clearance of cellular debris which may result in cytosolic accumulations and contribute to motor neuron injury (6). Español: Diagrama de los cambios más importantes en el la función del Retículo Endoplásmico, el aparato de Golgi, la señalización vía mTOR y la autofagia |
日期 | Published september 2008 |
來源 | PLoS ONE |
作者 | Philippe A. Parone |
此檔案採用創用CC 姓名標示 2.5 通用版授權條款。
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目前 | 2010年4月18日 (日) 19:03 | 2,067 × 1,435(1.15 MB) | Gustavocarra(留言 | 貢獻) | {{Information |Description={{en|1='''Summary of key gene expression changes to ER and Golgi function, vesicular transport, mTOR signalling and autophagy.'''<br/>The downregulation of multiple transcripts encoding ribosomal proteins, translation initiation |
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