Sandbox Reserved 709: Difference between revisions
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'''NPC'''s (''Nuclear Pore Complexes'') are composed of many [[Nucleoporin|nucleoporins]] and are heavy proteins assembly. These complexes allow the passive diffusion of ions and the active transport of large molecules such as proteins in both directions. Because of the particular shape of NPCs, transport of large proteins take a lot of time. | '''NPC'''s (''Nuclear Pore Complexes'') are composed of many [[Nucleoporin|nucleoporins]] and are heavy proteins assembly. These complexes allow the passive diffusion of ions and the active transport of large molecules such as proteins in both directions. Because of the particular shape of NPCs, transport of large proteins take a lot of time. | ||
Thus, proteins over 60 kDa have trouble to pass through them that’s why they need complementary proteins : ''' | Thus, proteins over 60 kDa have trouble to pass through them that’s why they need complementary proteins : '''importins''' to go in the nucleus and '''exportins''' to go out of the nucleus. <ref name="ALBERTS">ALBERTS,B. JOHNSON,A. WALTER,P. LEWIS,J. RAFF,M. ROBERTS,K. (2007). Molecular Biology of the Cell (p. 704-712)</ref> | ||
===Selectivity of nuclear import=== | ===Selectivity of nuclear import=== | ||
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===Cytoplasm to nucleus=== | ===Cytoplasm to nucleus=== | ||
[[Image:Nuclear_import_protein.png | 550px | right |thumb|Nuclear import of proteins through importins α and β]] | [[Image:Nuclear_import_protein.png | 550px | right |thumb|Nuclear import of proteins through importins α and β]] | ||
To initiate the transport to the nucleus, most of the NLS-containing proteins (or cargos) have to be recognized by a '''Nuclear Import Receptor'''. These are soluble cytosolic proteins such as '''importin α''' and ''' | To initiate the transport to the nucleus, most of the NLS-containing proteins (or cargos) have to be recognized by a '''Nuclear Import Receptor'''. These are soluble cytosolic proteins such as '''importin α''' and '''importin β'''. | ||
Import through NPC follows different steps : | Import through NPC follows different steps : | ||
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Once the import complex enters the nucleus, it must be '''dissociated''' to release the cargo protein. Then, importin α must be '''recycled''' to the cytoplasm. | Once the import complex enters the nucleus, it must be '''dissociated''' to release the cargo protein. Then, importin α must be '''recycled''' to the cytoplasm. | ||
* '''Step 4 :''' Cargo release is driven by ''' | * '''Step 4 :''' Cargo release is driven by '''Ran''', a '''G-protein''' that is found in '''Ran-GTP''' form in the nucleus due to a higher rate of RanGEF than RanGAP in chromatin. It binds to importin β, causing an important change in shape and reducing importin β affinity for '''importin α IBB'''. | ||
* '''Step 5 :''' Importin β can pass through the NPC thanks to Ran-GTP. A '''Ran-BP''' (''Ran-Binding Protein'') is a major component of the NPC’s cytoplasmic filaments. Thus, Ran-GTP is not released in the cytoplasm, but is still bound with importin β to the NPC. Ran-BP is also able to bind to a '''RanGAP'''. Finally, RanGAP locally promotes hydrolysis of '''Ran-GTP''' into '''Ran-GDP''', leading to its own release, and importin β release by the same. | * '''Step 5 :''' Importin β can pass through the NPC thanks to Ran-GTP. A '''Ran-BP''' (''Ran-Binding Protein'') is a major component of the NPC’s cytoplasmic filaments. Thus, Ran-GTP is not released in the cytoplasm, but is still bound with importin β to the NPC. Ran-BP is also able to bind to a '''RanGAP'''. Finally, RanGAP locally promotes hydrolysis of '''Ran-GTP''' into '''Ran-GDP''', leading to its own release, and importin β release by the same. | ||
* '''Step 6 :''' ''' | * '''Step 6 :''' '''Nup50''' (also called '''Npap60'''), a nucleoplasmin, weakens the link between '''importin α''' and the '''NLS''' of the cargo. Thus the cargo protein is now free in the nucleoplasm. | ||
* '''Step 7 :''' Importin α can’t leave the nucleus only with the help of Ran-GTP. It needs also interaction with ''' | * '''Step 7 :''' Importin α can’t leave the nucleus only with the help of Ran-GTP. It needs also interaction with '''CAS''' (''Cellular Apoptosis Susceptibility'' protein), an '''exportin''' which is similar in shape to importin β. Binding between CAS and importin α is favoured by interactions with Nup50. | ||
* '''Step 8 :'''The newly formed '''importin α:CAS:Ran-GTP''' complex is able to interact with nucleoplasmins of NPC, and once in the cytoplasm, Ran-GTP is hydrolysed into Ran-GDP (''see '''Step 5''' for details''). The complex splits, and importin α is now ready for a '''new import cycle'''.<ref name ="NUP50">PMID:16222336</ref> | * '''Step 8 :'''The newly formed '''importin α:CAS:Ran-GTP''' complex is able to interact with nucleoplasmins of NPC, and once in the cytoplasm, Ran-GTP is hydrolysed into Ran-GDP (''see '''Step 5''' for details''). The complex splits, and importin α is now ready for a '''new import cycle'''.<ref name ="NUP50">PMID:16222336</ref> | ||
