Sandbox Reserved 1653: Difference between revisions
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This central domain is surrounded by 3 extended arms called <scene name='86/868186/Blade/2'>blades</scene> extending out from the central pore in a rotatory manner <ref name ="Alexandra"> Zhou, Z. (2019). Structural Analysis of Piezo1 Ion Channel Reveals the Relationship between Amino Acid Sequence Mutations and Human Diseases. 139–155. DOI 10.4236/jbm.2019.712012 </ref>. | This central domain is surrounded by 3 extended arms called <scene name='86/868186/Blade/2'>blades</scene> extending out from the central pore in a rotatory manner <ref name ="Alexandra"> Zhou, Z. (2019). Structural Analysis of Piezo1 Ion Channel Reveals the Relationship between Amino Acid Sequence Mutations and Human Diseases. 139–155. DOI 10.4236/jbm.2019.712012 </ref>. | ||
"Each of these blades, deflecting at an angle of 100° perpendicular to the membrane, contains 6 tandems transmembranar helical units (THUs) constitute of 4 transmembrane domains".<ref name="mechanogating"/>,<ref name="Alexandra"/> "They are not planar: instead, they lie on a spherically curved surface with the membrane bulging into the cytoplasm".<ref name= "Piezo Senses Tension "> DOI 10.1016/j.cub.2018.02.078</ref> | "Each of these blades, deflecting at an angle of 100° perpendicular to the membrane, contains 6 tandems transmembranar helical units (THUs) constitute of 4 transmembrane domains".<ref name="mechanogating"/>,<ref name="Alexandra"/> "They are not planar: instead, they lie on a spherically curved surface with the membrane bulging into the cytoplasm".<ref name= "Piezo Senses Tension "> DOI 10.1016/j.cub.2018.02.078</ref> | ||
These flexible blades are inside the membrane and force the membrane to curve. That is why, they are considered as mechanotransduction modules, force sensors and transducers to gate the central pore. "These 3 blades propeller architecture is mechanically interesting because 3 blades are the minimum for omnidirectional sensitivity".<ref name="Piezo Senses Tension | These flexible blades are inside the membrane and force the membrane to curve. That is why, they are considered as mechanotransduction modules, force sensors and transducers to gate the central pore. "These 3 blades propeller architecture is mechanically interesting because 3 blades are the minimum for omnidirectional sensitivity".<ref name="Piezo Senses Tension "/> | ||
==='''CED or cap'''=== | ==='''CED or cap'''=== | ||
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The subcellular localisation of Piezo1 is also determining. In static conditions, its repartition is even on the membrane, but when a mechanical stimulus arises, Piezo1 accumulates at the cell’s apical. This process characterises endothelial cells’ alignment toward frictional force. | The subcellular localisation of Piezo1 is also determining. In static conditions, its repartition is even on the membrane, but when a mechanical stimulus arises, Piezo1 accumulates at the cell’s apical. This process characterises endothelial cells’ alignment toward frictional force. | ||
However, Piezo1 is also able to drive endothelial cells migration without shear stress, through endothelial [https://en.wikipedia.org/wiki/Nitric_oxide_synthasenitric oxide synthase], a protein with major roles in vascular biology.<ref name= "vascularisation"> DOI 10.1038/nature13701</ref> | However, Piezo1 is also able to drive endothelial cells migration without shear stress, through endothelial [https://en.wikipedia.org/wiki/Nitric_oxide_synthasenitric oxide synthase], a protein with major roles in vascular biology.<ref name= "vascularisation"> DOI 10.1038/nature13701</ref> | ||
== Diseases == | == Diseases == | ||
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Lymphatic dysplasia <ref name = "Lymphatic dysplasia"> DOI 10.1016/bs.ctm.2017.01.001 </ref> is also a disease linked to loss of function mutations on Piezo1. The [https://en.wikipedia.org/wiki/Lymphatic_system lymphatic system] is independent from the vascular one, and its role is to transport antigens responsible for the immune response. If the interstitial fluid is not drained correctly back to the blood, it leads to local inflammation. The mutations on Piezo1 inactivate the channel gate and in this case the concentration of calcium is not increased. The protein isn’t sensitive to the pressure anymore. | Lymphatic dysplasia <ref name = "Lymphatic dysplasia"> DOI 10.1016/bs.ctm.2017.01.001 </ref> is also a disease linked to loss of function mutations on Piezo1. The [https://en.wikipedia.org/wiki/Lymphatic_system lymphatic system] is independent from the vascular one, and its role is to transport antigens responsible for the immune response. If the interstitial fluid is not drained correctly back to the blood, it leads to local inflammation. The mutations on Piezo1 inactivate the channel gate and in this case the concentration of calcium is not increased. The protein isn’t sensitive to the pressure anymore. | ||
== Potential therapeutic target == | == Potential therapeutic target == | ||
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== Relevance == | == Relevance == | ||
A majority of Piezo1’s structure has been resolved by [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryo-em] but still information is lacking on the N-term domain and some subregions. There is no full structure available yet which can be troublesome to understand the mechanism of the protein. Moreover, Piezo1 is present in a large number of tissues, but the differences in its roles are unclear. Further research is required to allow a better understanding of diseases linked to Piezo1 (like DHS), and thus a better treatment of those diseases. | |||
[http://www.rcsb.org/structure/5Z10 PBD] | [http://www.rcsb.org/structure/5Z10 PBD] | ||
