Morphogenesis of ellipsoidal camelid red cells : a possible role of a hyperstable membrane skeleton due to a novel alternatively spliced 4.1R

概要

Although cell shape and function are intrinsically coupled, the shapes of red blood cells
(RBCs) in vertebrate species are highly diverse, despite these cells sharing a common function
in efficient gas exchange in all vertebrates. Vertebrate RBCs have evolved into two basic shapes.
All nonmammalian RBCs have a biconvex ellipsoidal shape and are nucleated (Lazarides, 1987;
Lazarides and Woods, 1989). Besides the shape, the average RBC size in all camelid species is
smaller than most other domestic species with mean corpuscular volumes (MCVs). The mean
corpuscular hemoglobin concentration (MCHC) of camelids is generally higher. The size and
shape of camelid RBCs facilitate oxygen diffusion by providing a higher effective surface area
for gas exchange (Tornquist, 2022). The generation and maintenance of this elliptical shape of
nonmammalian RBCs are likely result from co-operative and anisotropic interactions of the
plasma membrane-associated membrane skeleton and the transcellular cytoskeleton, involving
both intermediate filaments and microtubules (Lazarides, 1987). In contrast, due to the absence
of a transcellular cytoskeleton, nucleus, and intracellular organelles, the shape of mammalian
RBCs depends exclusively on their plasma membranes, with uniform membrane skeletal
structure across the entire surface (Fowler, 2013). The resultant RBCs of most mammalian
species have a biconcave disk shape under the hydrostatic conditions and undergo extensive
and repeated deformation under shear stress during transit through the microvasculature,
resulting in efficient gas and ion transport (Gallagher, 2004; Salomao et al., 2008; Callagher,
2017). However, the evolutionary molecular basis for the difference between ellipsoidal and
discoidal shaped of RBCs remains unclear.
Intriguingly, camelid RBCs differ in shape from other RBCs. In contrast to other
mammalian species, mature RBCs (erythrocytes) of camelid species are flat ellipsoids with
markedly reduced membrane deformability in response to applied shear stress (Smith et al.,
1980). ...

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