Sandbox Reserved 485: Difference between revisions
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==Mechanism of Action== | ==Mechanism of Action== | ||
===Ran Cycle: Import and Export=== | |||
[[Image:Ran cycle.jpg | thumb]] | [[Image:Ran cycle.jpg | thumb]] | ||
The Ran cycle plays a major function in translocating cargo such as RNA and proteins from and to the cytoplasm and nucleus. Cargo that is imported are typically proteins that are synthesized in the cytoplasm but function in the nucleus. A receptor protein known as an importin recognizes and binds to the nuclear localization signal, NLS, located on the cytoplasmic cargo. Importin-NLS protein complex is then able to be transported from the cytoplasm through the nuclear pore complex into the nucleus. Once inside the nucleus, the importin binds to Ran-GTP, allowing the release of the protein from the importin. The Ran-GTP-importin complex migrates back through the nuclear pore complex to release the importin back into the cytosplasm for reuse as Ran-GTP is hydrolyzed to Ran-GDP. | The Ran cycle plays a major function in translocating cargo such as RNA and proteins from and to the cytoplasm and nucleus. Cargo that is imported are typically proteins that are synthesized in the cytoplasm but function in the nucleus. A receptor protein known as an importin recognizes and binds to the nuclear localization signal, NLS, located on the cytoplasmic cargo. Importin-NLS protein complex is then able to be transported from the cytoplasm through the nuclear pore complex into the nucleus. Once inside the nucleus, the importin binds to Ran-GTP, allowing the release of the protein from the importin. The Ran-GTP-importin complex migrates back through the nuclear pore complex to release the importin back into the cytosplasm for reuse as Ran-GTP is hydrolyzed to Ran-GDP. | ||
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The key to the import and export of cargo material is dependent on the concentration of Ran-GTP. The concentration of Ran-GTP is maintained by guanine-nucleotide exchange factor, GEF, in the nucleus and a GTPase activating protein, GAP, in the cytosol. Cellular signals indicate the course of the Ran cycle and is especially significant while entering mitosis. | The key to the import and export of cargo material is dependent on the concentration of Ran-GTP. The concentration of Ran-GTP is maintained by guanine-nucleotide exchange factor, GEF, in the nucleus and a GTPase activating protein, GAP, in the cytosol. Cellular signals indicate the course of the Ran cycle and is especially significant while entering mitosis. | ||
== | ===Regulation of Mitosis=== | ||
Ran also serves a variety of other functions such as mediating DNA synthesis and advancements through a cell cycle. During prophase the RanGTP-RanGDP gradient from the nucleus to cytoplasm is high, resulting in th ebreakdown of the nuclear envelope. Nup358 and other Ran associated proteins are directed to the kinetochores to directthe attachment of spindle fibers to chromosomes. RanGTP further activates the assembly of the spindle by releasing and activating the spindle assembly factors, NuMA and TPX2. | |||
During telophase the RanGTP is hydrolyzed to reform the daughter nuclei's nuclear envelope. | |||
Ran regulates these functions by directing the formation and organization of the microtubule complex. Ran-GTP promotes spindle assembly and the spindle fiber’s attachment to the chromosome. Ran is also involved in activating T cells and the reassembly of the nuclear envelope during mitosis. | |||
==Possible Applications== | |||
It is obvious the importance Ran plays within the cell cycle. Defective Ran protein results in irregular reformation of the nuclear envelope, chromosome assembly and microtubule formation. Within the nucleus, malfunctions pertaining to factors associated with specific functions such as splicing and DNA replication These misregulations can result in immunodeficient disorders or X-linked mental retardation. Further research is being conducted to fully understand Ran’s mechanism and regulatory measures. | It is obvious the importance Ran plays within the cell cycle. Defective Ran protein results in irregular reformation of the nuclear envelope, chromosome assembly and microtubule formation. Within the nucleus, malfunctions pertaining to factors associated with specific functions such as splicing and DNA replication These misregulations can result in immunodeficient disorders or X-linked mental retardation. Further research is being conducted to fully understand Ran’s mechanism and regulatory measures. | ||
