E-viri
-
Smith, Alyson S
01/2018Dissertation
The biconcave disk shape, deformability, and resiliency of the mammalian red blood cell (RBC) are vital to its circulatory function. These features rely on the membrane skeleton, a viscoelastic network of short, membrane-associated actin filaments (F-actin) cross-linked by long, flexible spectrin tetramers. RBCs contain nonmuscle myosin II (NMII), an F-actin-activated ATPase that exerts force on F-actin networks in many cells types to control cell shapes and membrane properties. However, a function for NMII contractility in RBCs has not previously been tested. The work presented in this thesis shows that nonmuscle myosin IIA (NMIIA) forms bipolar filaments that interact with the membrane skeleton to control RBC membrane curvature and deformability. MgATP disrupts NMIIA association with the membrane skeleton, consistent with NMIIA motor domains binding to F-actin, and the phosphorylation of RBC NMIIA heavy and light chains indicate active regulation of NMIIA motor activity and filament assembly. Inhibition of NMII motor activity with blebbistatin demonstrates a role for this activity in NMIIA-membrane association, nanoscale membrane oscillations, membrane curvature, and RBC deformability. Characterization of RBC phenotypes in patients with NMIIA heavy chain mutations shows that patients with motor domain mutations have the most severe, phenotypes, further supporting the role of this domain in RBC NMIIA function. While patients do not have clinically significant anemias, patient RBCs exhibit abnormal morphologies and hematological indices. Some mutations affect NMIIA association with the membrane skeleton and regulation of filament assembly through heavy chain phosphorylation, likely contributing to these phenotypes. Together, these data indicate a role for NMIIA contractility in promoting membrane stiffness and maintaining RBC biconcave disk shape. As structures similar to the RBC membrane skeleton exist in many metazoan cell types, these results demonstrate a general function for NMII in controlling membrane morphology and mechanical properties through contractile interactions with spectrin-F-actin networks.
Avtor
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.