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Current Biology : CB Dec 2021Cytokinesis, the process that partitions the mother cell into two daughter cells, requires the assembly and constriction of an equatorial actomyosin network. Different...
Cytokinesis, the process that partitions the mother cell into two daughter cells, requires the assembly and constriction of an equatorial actomyosin network. Different types of non-motor F-actin crosslinkers localize to the network, but their functional contribution remains poorly understood. Here, we describe a synergy between the small rigid crosslinker plastin and the large flexible crosslinker spectrin in the C. elegans one-cell embryo. In contrast to single inhibitions, co-inhibition of plastin and the βH-spectrin (SMA-1) results in cytokinesis failure due to progressive disorganization and eventual collapse of the equatorial actomyosin network. Cortical localization dynamics of non-muscle myosin II in co-inhibited embryos mimic those observed after drug-induced F-actin depolymerization, suggesting that the combined action of plastin and spectrin stabilizes F-actin in the contractile ring. An in silico model predicts that spectrin is more efficient than plastin at stabilizing the ring and that ring formation is relatively insensitive to βH-spectrin length, which is confirmed in vivo with a sma-1 mutant that lacks 11 of its 29 spectrin repeats. Our findings provide the first evidence that spectrin contributes to cytokinesis and highlight the importance of crosslinker interplay for actomyosin network integrity.
Topics: Actins; Actomyosin; Animals; Caenorhabditis elegans; Cytokinesis; Membrane Glycoproteins; Microfilament Proteins; Spectrin
PubMed: 34666005
DOI: 10.1016/j.cub.2021.09.055 -
Brain Research Bulletin 1995This article reviews our current knowledge of the structure of alpha spectrins and beta spectrins in the brain, as well as their location and expression within neural... (Review)
Review
This article reviews our current knowledge of the structure of alpha spectrins and beta spectrins in the brain, as well as their location and expression within neural tissue. We discuss the known protein interactions of brain spectrin isoforms, and then describe results that suggest an important role for spectrin (alpha SpII sigma 1/beta SpII sigma 1) in the Ca(2+)-regulated release of neurotransmitters. Evidence that supports a role for spectrin in the docking of synaptic vesicles to the presynaptic plasma membrane and as a Ca2+ sensor protein that unclamps the fusion machinery is described, along with the Casting the Line model, which summarizes the information. We finish with a discussion of the value of spectrin and ankyrin-deficient mouse models in deciphering spectrin function in neural tissue.
Topics: Amino Acid Sequence; Animals; Brain; Brain Chemistry; Embryonic and Fetal Development; Humans; Mice; Mice, Mutant Strains; Molecular Sequence Data; Molecular Structure; Spectrin
PubMed: 7757495
DOI: 10.1016/0361-9230(94)00264-2 -
BioEssays : News and Reviews in... Aug 2006Recently, betaIII spectrins have been recognized as ataxia disease genes, with the identification by Ikeda and co-workers of pathogenic mutations in the SPTBN2 gene in... (Review)
Review
Recently, betaIII spectrins have been recognized as ataxia disease genes, with the identification by Ikeda and co-workers of pathogenic mutations in the SPTBN2 gene in three large (and mapped) SCA5 families of American and European origin.((1)) With their discovery, the large "Lincoln" family has been traced back to the underlying genetic defect for the slowly progressive cerebellar ataxia. In addition, the involvement of this component of the cytoskeleton directs attention towards the possible role of organelle stability during neurodegeneration. The findings suggest that the mechanical properties of neurons and their dynamics may be as important as altered Ca(2+) homeostasis, transcriptional dysregulation, and impaired protein degradation in neurodegeneration conditions.
Topics: Humans; Mutation; Nerve Degeneration; Spectrin; Spinocerebellar Ataxias
PubMed: 16927298
DOI: 10.1002/bies.20443 -
Biophysical Journal Sep 2021Spectrin tetramers of the membranes of enucleated mammalian erythrocytes play a critical role in red blood cell survival in circulation. One of the spectrins, αI,...
Spectrin tetramers of the membranes of enucleated mammalian erythrocytes play a critical role in red blood cell survival in circulation. One of the spectrins, αI, emerged in mammals with enucleated red cells after duplication of the ancestral α-spectrin gene common to all animals. The neofunctionalized αI-spectrin has moderate affinity for βI-spectrin, whereas αII-spectrin, expressed in nonerythroid cells, retains ancestral characteristics and has a 10-fold higher affinity for βI-spectrin. It has been hypothesized that this adaptation allows for rapid make and break of tetramers to accommodate membrane deformation. We have tested this hypothesis by generating mice with high-affinity spectrin tetramers formed by exchanging the site of tetramer formation in αI-spectrin (segments R0 and R1) for that of αII-spectrin. Erythrocytes with αIIβI presented normal hematologic parameters yet showed increased thermostability, and their membranes were significantly less deformable; under low shear forces, they displayed tumbling behavior rather than tank treading. The membrane skeleton is more stable with αIIβI and shows significantly less remodeling under deformation than red cell membranes of wild-type mice. These data demonstrate that spectrin tetramers undergo remodeling in intact erythrocytes and that this is required for the normal deformability of the erythrocyte membrane. We conclude that αI-spectrin represents evolutionary optimization of tetramer formation: neither higher-affinity tetramers (as shown here) nor lower affinity (as seen in hemolytic disease) can support the membrane properties required for effective tissue oxygenation in circulation.
Topics: Animals; Biological Evolution; Erythrocyte Deformability; Erythrocyte Membrane; Erythrocytes; Mice; Spectrin
PubMed: 34352252
DOI: 10.1016/j.bpj.2021.07.027 -
BioEssays : News and Reviews in... Nov 1998Spectrin, together with actin and a number of other accessory proteins, forms a submembrane cytoskeletal network in the human erythrocyte ghost. Through an elegant... (Review)
Review
Spectrin, together with actin and a number of other accessory proteins, forms a submembrane cytoskeletal network in the human erythrocyte ghost. Through an elegant combination of structural, biochemical, and genetic studies, spectrin was shown to be an important determinant of erythrocyte shape and membrane stability. Genetic studies of a novel nonerythroid spectrin (beta H) in Drosophila and Caenorhabditis elegans now reveal that spectrin can influence the shape and stability of whole organisms. Nonerythroid spectrins are proposed to have roles in cell adhesion, establishment of cell polarity, and attachment of other cytoskeletal structures to the plasma membrane. The phenotypes of the beta H spectrin mutations provide an exciting biological context in which to evaluate these roles and perhaps to uncover new ones.
Topics: Animals; Caenorhabditis elegans; Cytoskeletal Proteins; Drosophila; Drosophila Proteins; Erythrocyte Membrane; Erythrocytes; Humans; Spectrin
PubMed: 9872052
DOI: 10.1002/(SICI)1521-1878(199811)20:11<875::AID-BIES1>3.0.CO;2-P -
Postepy Biochemii 2012Membrane skeleton is a structure that provides strength and elasticity to the erythrocyte membrane. This features stem from the main component of this structure, a... (Review)
Review
Membrane skeleton is a structure that provides strength and elasticity to the erythrocyte membrane. This features stem from the main component of this structure, a multifunctional protein called spectrin. Spectrin forms a network underlying membrane bilayer containing integral membrane proteins which interact with multiple proteins and lipid partners. Although membrane skeleton and spectrin structure have been described before, the latest discoveries show their new details and properties. In this work we summarize recent findings concerning structure and function of spectrin together with its possible role in pathology. We focus our interest on lately published structural data and we make an attempt to combine these findings with possible physiological functions.
Topics: Animals; Erythrocyte Membrane; Humans; Models, Molecular; Spectrin
PubMed: 23373410
DOI: No ID Found -
Current Biology : CB May 2021Lindsay Teliska and Matthew Rasband introduce spectrins - cytoskeletal proteins that localise to the inner face of the plasma membrane and serve a scaffolding function...
Lindsay Teliska and Matthew Rasband introduce spectrins - cytoskeletal proteins that localise to the inner face of the plasma membrane and serve a scaffolding function between membrane proteins and the actin cortex.
Topics: Actins; Cell Membrane; Membrane Proteins; Spectrin
PubMed: 34033780
DOI: 10.1016/j.cub.2021.01.040 -
Blood Cells 1987The group of disorders manifesting as hereditary elliptocytosis/pyropoikilocytosis (HE/HPP) represent a unique group of experiments of nature that result from molecular... (Review)
Review
The group of disorders manifesting as hereditary elliptocytosis/pyropoikilocytosis (HE/HPP) represent a unique group of experiments of nature that result from molecular defects of alpha spectrin. At the level of protein structure, these alpha spectrins can be identified by analysis of peptides generated by limited tryptic digestion. Such an approach reveals that the peptide containing alpha spectrin self-association site (the alpha I domain, molecular mass of 80 daltons) is cleaved to peptides of smaller size, presumably due to changes in the primary structure that lead to increased susceptibility of existing cleavage sites or the opening of new sites. Based on the mass of these peptides, we designate these alpha spectrin (Sp) mutants, Sp alpha 1/74, Sp alpha 1/65, and Sp alpha 1/46. At the level of protein function, these mutant alpha spectrins are characterized by a defective self-association of spectrin heterodimers to tetramers, the major structural subunits of the skeleton. One of the most interesting features of this group of disorders is a variable severity of their clinical expression. Molecular determinants of disease severity include the percentage of unassembled, that is, dimeric spectrin in the membrane and the total spectrin content in the cells. Consequently, the most severely affected patients, manifesting as HPP, contain a high fraction of unassembled, dimeric spectrin in the membrane (55 +/- 7%) and are, in addition, partially deficient in spectrin. In contrast, HE individuals and asymptomatic carriers have a moderate (33 +/- 11) or mild (24 +/- 9) increase in spectrin dimers (normals 5 +/- 4%) and they contain normal amounts of spectrin in their membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Elliptocytosis, Hereditary; Erythrocyte Membrane; Erythrocytes, Abnormal; Humans; Models, Biological; Peptide Fragments; Peptide Hydrolases; Protein Conformation; Spectrin
PubMed: 3311220
DOI: No ID Found -
Chemistry and Physics of Lipids Jun 2006The object of this paper is to review briefly the studies on the interactions of erythroid and non-erythroid spectrins with lipids in model and natural membranes. An... (Review)
Review
The object of this paper is to review briefly the studies on the interactions of erythroid and non-erythroid spectrins with lipids in model and natural membranes. An important progress on the identification of lipid-binding sites has recently been made although many questions remain still unanswered. In particular, our understanding of the physiological role of such interactions is still limited. Another important issue is the occurrence of spectrins in membrane rafts, how they are attached to the raft and what is their function in rafts.
Topics: Binding Sites; Cell Membrane; Erythroid Cells; Membrane Lipids; Phospholipids; Spectrin
PubMed: 16566912
DOI: 10.1016/j.chemphyslip.2006.02.008 -
Biochimica Et Biophysica Acta Aug 1998The existence of a Golgi-localized membrane cytoskeleton has been revealed by the identification of two major components of the spectrin membrane skeleton, spectrin and... (Review)
Review
The existence of a Golgi-localized membrane cytoskeleton has been revealed by the identification of two major components of the spectrin membrane skeleton, spectrin and ankyrin, that associate with the Golgi complex. Golgi spectrin was identified with an antibody specific for the beta-subunit of the erythroid isoform of spectrin (beta1Sigma1). This antibody recognizes a 220 kDa polypeptide that localizes to discrete regions of the Golgi complex and associates with Golgi membranes in a Brefeldin A sensitive manner. Two isoforms of Golgi ankyrin have been identified: a 119 kDa form (AnkG119) which represents a truncated, alternatively spliced isoform of a recently cloned novel ankyrin of the nervous system AnkG, and a larger 195 kDa ankyrin (Ank195) that cross-reacts with antibodies to erythrocyte ankyrin. A Golgi localized membrane skeleton composed of these unique membrane skeleton isoforms could serve a variety of important functions, including the maintenance of Golgi structural organization and the formation of discrete membrane domains within Golgi compartments.
Topics: Animals; Cytoskeleton; Golgi Apparatus; Humans; Intracellular Membranes; Membrane Proteins; Spectrin
PubMed: 9714784
DOI: 10.1016/s0167-4889(98)00054-8