The spectrin skeleton: from red cells to brain.

Bennett, Vann; Lambert, Stephen

doi:10.1172/jci115157

Cited by 106 publications

(55 citation statements)

References 69 publications

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“…The actin-based cytoskeleton is a dynamic intracellular structure that plays an essential role in the regulation of cellular events, including the stability of cell shape, the onset of cell motility (38), and the distribution of integral membrane proteins (7,10,39,40). The hypothesis that the actin cytoskeleton is directly involved in the regulation of epithelial Na ϩ channels was first suggested by immunocolocalization studies showing that Na ϩ channels are always in close proximity to actin filaments (15,22).…”

Section: Discussionmentioning

confidence: 99%

“…Actin networks interact with the plasma membrane either by direct binding (3, 4) or through anchoring proteins, including actin-binding protein (filamin), spectrin (fodrin, the non-erythroid form of spectrin), and ankyrin (5)(6)(7)(8). The actin cytoskeleton has been shown to interact with a variety of transmembrane proteins, including ion transport molecules such as the band 3 anion exchanger (9), the epithelial Na ϩ /K ϩ -ATPase (6,10), rat brain voltage-sensitive Na ϩ channels (11,12), the Na ϩ -K ϩ -Cl Ϫ cotransporter (13), and the Na ϩ -H ϩ exchanger (14).…”

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confidence: 99%

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Regulation of Epithelial Sodium Channels by Short Actin Filaments

Berdiev

Prat

Cantiello

et al. 1996

Journal of Biological Chemistry

149

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Cytoskeletal elements play an important role in the regulation of ion transport in epithelia. We have studied the effects of actin filaments of different length on the ␣, ␤, ␥-rENaC (rat epithelial Na ؉ channel) in planar lipid bilayers. We found the following. 1) Short actin filaments caused a 2-fold decrease in unitary conductance and a 2-fold increase in open probability (P o ) of ␣,␤,␥-rENaC. 2) ␣,␤,␥-rENaC could be transiently activated by protein kinase A (PKA) plus ATP in the presence, but not in the absence, of actin. 3) ATP in the presence of actin was also able to induce a transitory activation of ␣,␤,␥-rENaC, although with a shortened time course and with a lower magnitude of change in P o . 4) DNase I, an agent known to prohibit elongation of actin filaments, prevented activation of ␣,␤,␥-rENaC by ATP or PKA plus ATP. 5) Cytochalasin D, added after rundown of ␣,␤,␥-rENaC activity following ATP or PKA plus ATP treatment, produced a second transient activation of ␣,␤,␥-rENaC. 6) Gelsolin, a protein that stabilizes polymerization of actin filaments at certain lengths, evoked a sustained activation of ␣,␤,␥-rENaC at actin/gelsolin ratios of <32:1, with a maximal effect at an actin/gelsolin ratio of 2:1. These results suggest that short actin filaments activate ␣,␤,␥-rENaC. PKA-mediated phosphorylation augments activation of this channel by decreasing the rate of elongation of actin filaments. These results are consistent with the hypothesis that cloned ␣,␤,␥-rENaCs form a core conduction unit of epithelial Na ؉ channels and that interaction of these channels with other associated proteins, such as short actin filaments, confers regulation to channel activity.Membrane transport protein-cytoskeleton interactions are thought to be important not only for restricting various transporters to specific membrane domains, especially in epithelia, but also for regulating transport activity (1, 2). Actin networks interact with the plasma membrane either by direct binding (3, 4) or through anchoring proteins, including actin-binding protein (filamin), spectrin (fodrin, the non-erythroid form of spectrin), and ankyrin (5-8). The actin cytoskeleton has been shown to interact with a variety of transmembrane proteins, including ion transport molecules such as the band 3 anion exchanger (9), the epithelial Na ϩ /K ϩ -ATPase (6, 10), rat brain voltage-sensitive Na ϩ channels (11, 12), the Na ϩ -K ϩ -Cl Ϫ cotransporter (13), and the Na ϩ -H ϩ exchanger (14). Recently, functional interactions between the actin cytoskeleton and ion channels have been demonstrated for Na ϩ channel activity in epithelial cells (15), N-methyl-D-aspartic acid-activated channels in neurons (16), the Na ϩ /K ϩ -ATPase (17), a renal K ϩ channel (18), and two epithelial anion channels (namely, a renal Cl Ϫ channel (19) and the cystic fibrosis transmembrane conductance regulator (20, 21)). Apically located, renal amiloride-sensitive Na ϩ channels have also been shown to be associated directly with the actin-based membrane cytoskeleton (15, 22). Moreov...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Regulation of Epithelial Sodium Channels by Short Actin Filaments

Berdiev

Prat

Cantiello

et al. 1996

Journal of Biological Chemistry

149

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“…This surprising correspondence with the time course of LTP consolidation is suggestive of a causal relationship, in which some set of events stabilizes newly assembled actin filaments and thereby stabilizes the new spine morphologies they support. The most likely candidate for a consolidation process of this type is cross-linking of the actin filaments, a function executed by a handful of proteins, the most prominent of which is spectrin (Goodman and Zagon, 1986;Fox et al, 1987;Bennett and Lambert, 1991) and its homologues. Spectrin is concentrated in adult brain membranes (Siman et al, 1987) and theta burst stimulation, applied at threshold levels for inducing LTP, causes its proteolysis , evidently through activation of the calcium sensitive protease calpain (Bednarski et al, 1995;Vanderklish et al, 1995Vanderklish et al, , 1996.…”

Section: Consolidationmentioning

confidence: 99%

Synaptic plasticity in early aging

Lynch

Rex

Gall

2006

Ageing Research Reviews

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Studies of how aging affects brain plasticity have largely focused on old animals. However, deterioration of memory begins well in advance of old age in animals, including humans; the present review is concerned with the possibility that changes in synaptic plasticity, as found in the long-term potentiation (LTP) effect, are responsible for this. Recent results indicate that impairments to LTP are in fact present by early middle age in rats but only in certain dendritic domains. The search for the origins of these early aging effects necessarily involves ongoing analyses of how LTP is induced, expressed, and stabilized. Such work points to the conclusion that cellular mechanisms responsible for LTP are redundant and modulated both positively and negatively by factors released during induction of potentiation. Tests for causes of the localized failure of LTP during early aging suggest that the problem lies in excessive activity of a negative modulator. The view of LTP as having redundant and modulated substrates also suggests a number of approaches for reversing age-related losses. Particular attention will be given to the idea that induction of brain-derived neurotrophic factor, an extremely potent positive modulator, can be used to provide long periods of normal plasticity with very brief pharmacological interventions. The review concludes with a consideration of how the selective, regional deficits in LTP found in early middle age might be related to the global phenomenon of brain aging. #

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“…This protein is discharged by the invading merozoite and exported to the Pf-RBC membrane where, once phosphorylated, it interacts with the spectrin network (13). Because spectrin plays a critical role in the ability of RBCs to deform (14,15), it has been proposed that RESA could play an important role in the modulation of mechanical properties of ring-stage Pf-RBCs (1,6). A connection between RESA and altered Pf-RBC mechanical properties has been demonstrated in a previous study on Pf-RBC membrane stability.…”

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confidence: 99%

Effect of plasmodial RESA protein on deformability of human red blood cells harboring Plasmodium falciparum

Mills¹,

Diez-Silva

Quinn

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

179

166

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During intraerythrocytic development, Plasmodium falciparum exports proteins that interact with the host cell plasma membrane and subplasma membrane-associated spectrin network. Parasiteexported proteins modify mechanical properties of host RBCs, resulting in altered cell circulation. In this work, optical tweezers experiments of cell mechanical properties at normal physiological and febrile temperatures are coupled, for the first time, with targeted gene disruption techniques to measure the effect of a single parasite-exported protein on host RBC deformability. We investigate Pf155/Ring-infected erythrocyte surface antigen (RESA), a parasite protein transported to the host spectrin network, on deformability of ring-stage parasite-harboring human RBCs. Using a set of parental, gene-disrupted, and revertant isogenic clones, we found that RESA plays a major role in reducing deformability of host cells at the early ring stage of parasite development, but not at more advanced stage. We also show that the effect of RESA on deformability is more pronounced at febrile temperature, which ring-stage parasite-harboring RBCs can be exposed to during a malaria attack, than at normal body temperature. malaria ͉ erythrocyte ͉ membrane shear modulus ͉ spectrin ͉ cytoskeleton A fter Plasmodium falciparum merozoite invasion of a human RBC, the parasite differentiates and multiplies for 48 h, leading to rupture of the parasitized RBC (Pf-RBCs) and release of new merozoites in the blood circulation. Throughout this 48-h period, several parasite proteins are introduced into the RBC plasma membrane and submembranous protein skeleton, thereby modifying a range of structural and functional properties of the Pf-RBCs (1-4). The best documented changes occur as P. falciparum matures to the trophozoite (24-36 h) and schizont (36-48 h) stages, when Pf-RBCs display decreased membrane deformability (2-6), become spherical, and develop cytoadherence properties responsible for parasite sequestration in the postcapillary venules of different organs (7,8). In contrast, during early parasite development, ring-stage (0-24 h after invasion) Pf-RBCs preserve their biconcave shape, can circulate in peripheral blood (9), and thus are exposed to the spleen red pulp. Ring-stage Pf-RBCs may pass through this spleen compartment, be expelled from circulation, or return to the circulation once the parasite has been removed (10). Although the relative importance of these different processes and their underlying mechanisms are not fully understood, it is likely that altered deformability of ring-stage Pf-RBCs (11) plays a crucial role in determining Pf-RBCs spleen processing.Introduction of parasite components within the Pf-RBC membrane and cortical cytoskeleton begins soon after RBC invasion, as demonstrated for the well characterized parasite protein Pf155/Ring-infected erythrocyte surface antigen (RESA) (12). This protein is discharged by the invading merozoite and exported to the Pf-RBC membrane where, once phosphorylated, it interacts with the spectrin n...

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The spectrin skeleton: from red cells to brain.

Cited by 106 publications

References 69 publications

Regulation of Epithelial Sodium Channels by Short Actin Filaments

Regulation of Epithelial Sodium Channels by Short Actin Filaments

Synaptic plasticity in early aging

Effect of plasmodial RESA protein on deformability of human red blood cells harboring Plasmodium falciparum

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