Compartmentalization of sickle-cell calcium in endocytic inside-out vesicles

Much recent interest in the mechanism of dehydration of the dense subpopulation of sickle-cell anaemia (SS) red cells, including the 'irreversibly sickled cells' (ISCs), stems from the view that these relatively rigid cells have a major role in the two main clinical features of the disease, namely haemolytic anaemia and microvascular occlusion. The discovery that SS red cells have an elevated calcium content and accumulate Ca2+ during deoxygenation-induced sickling suggested a working hypothesis of wide appeal for the mechanism of cell dehydration: retained calcium would activate the red cell Ca2+-sensitive K+ channels, causing progressive net loss of KCl and water. However, retained calcium, which seemed as weakly bound to cytoplasmic buffers as in normal red cells, failed to show any measurable activation of K+ channels or Ca2+ pumps in metabolically normal SS cells, despite the apparent functional normality or near-normality of these transport systems. We now offer a possible explanation for this failure. We show that, contrary to the traditional views, SS cells, and to a lesser extent normal human red cells, possess intracellular vesicles with ATP-dependent Ca2+-accumulating capacity, and that nearly all the measurable calcium of fresh SS cells is contained within such vesicles, probably in the form of precipitates with inorganic or organic phosphates.     

Convergent evolution in mechanical design of lamnid sharks and tunas

The evolution of 'thunniform' body shapes in several different groups of vertebrates, including whales, ichthyosaurs and several species of large pelagic fishes supports the view that physical and hydromechanical demands provided important selection pressures to optimize body design for locomotion during vertebrate evolution. Recognition of morphological similarities between lamnid sharks (the most well known being the great white and the mako) and tunas has led to a general expectation that they also have converged in their functional design; however, no quantitative data exist on the mechanical performance of the locomotor system in lamnid sharks. Here we examine the swimming kinematics, in vivo muscle dynamics and functional morphology of the force-transmission system in a lamnid shark, and show that the evolutionary convergence in body shape and mechanical design between the distantly related lamnids and tunas is much more than skin deep; it extends to the depths of the myotendinous architecture and the mechanical basis for propulsive movements. We demonstrate that not only have lamnids and tunas converged to a much greater extent than previously known, but they have also developed morphological and functional adaptations in their locomotor systems that are unlike virtually all other fishes.     

The parvins

The parvins are a family of proteins involved in linking integrins and associated proteins with intracellular pathways that regulate actin cytoskeletal dynamics and cell survival. Both α-parvin (PARVA) and β-parvin (PARVB) localize to focal adhesions and function in cell adhesion, spreading, motility and survival through interactions with partners, such as integrin-linked kinase (ILK), paxillin, α-actinin and testicular kinase 1. A complex of PARVA with ILK and the LIM protein PINCH-1 is critical for cell survival in a variety of cells, including certain cancer cells, kidney podocytes and cardiac myocytes. While PARVA inhibits the activities of Rac1 and testicular kinase 1 and cell spreading, PARVB binds αPIX and α-actinin, and can promote cell spreading. In contrast to PARVA, PARVB inhibits ILK activity and reverses some of its oncogenic effects in cancer cells. This review focuses on the structure and function of the parvins and some possible roles in human diseases. Received 5 August 2005; received after revision 5 September 2005; accepted 22 September 2005