Sandbox Reserved 1653: Difference between revisions
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== Disease == | == Disease == | ||
[https://en.wikipedia.org/wiki/Hereditary_stomatocytosis Dehydrated hereditary stomatocytosis] (DHS) is a genetic disease with impaired red blood cell (RBC) membrane properties that affect intracellular cation concentrations. | [https://en.wikipedia.org/wiki/Hereditary_stomatocytosis Dehydrated hereditary stomatocytosis] (DHS) is a genetic disease with impaired red blood cell (RBC) membrane properties that affect intracellular cation concentrations. <ref name="Dehydrated"> DOI 10.1038/ncomms2899</ref> The RBCs are abnormally shaped and they result in [https://en.wikipedia.org/wiki/Hemolytic_anemia haemolytic anaemia]. | ||
Piezo1 is expressed in the plasma membranes of RBCs, and its role is to control RBCs’s osmolarity. It also plays a prevalent role in the [https://en.wikipedia.org/wiki/Erythropoiesis erythroid differentiation]. Mutations in PIEZO1 distort mechanosensitive channel regulation, leading to increased cation transport in [https://en.wikipedia.org/wiki/Red_blood_cell erythroid cells]. | Piezo1 is expressed in the plasma membranes of RBCs, and its role is to control RBCs’s osmolarity. It also plays a prevalent role in the [https://en.wikipedia.org/wiki/Erythropoiesis erythroid differentiation]. Mutations in PIEZO1 distort mechanosensitive channel regulation, leading to increased cation transport in [https://en.wikipedia.org/wiki/Red_blood_cell erythroid cells]. | ||
According to studies, piezo1 mutations are the cause of DHS. | According to studies, piezo1 mutations are the cause of DHS.<ref name="Multiple clinical"> DOI 10.1182/blood-2013-02-482489</ref> Those mutations could provoke increases in permeability of cations in RBC by different mechanisms. It could induce mechanically activated currents that inactivate more slowly than wild-type currents. They could also affect the inactivation process by either destabilising the inactivated state or stabilising the channel in the open state. As a result, the open to inactivated state equilibrium shifts towards open. Na+ and Ca2+ ion influx consequently increases, and the intracellular K+ concentration decreases in a steady state. | ||
The evolution of piezo1’s function steams from a change in its 3D structure. All the dehydrated hereditary stomatocytosis-associated mutations locate at C-terminal half of PIEZO1, but the way it affects piezo1’s structure is yet to be fully understood. | The evolution of piezo1’s function steams from a change in its 3D structure. All the dehydrated hereditary stomatocytosis-associated mutations locate at C-terminal half of PIEZO1, but the way it affects piezo1’s structure is yet to be fully understood.<ref name = "Dehydrated"/> | ||
== Relevance == | == Relevance == | ||
