Spectrin-like proteins

Hemphill, A., Seeback, T. and Lawson, D. (1991) The Trypanosoma brucei cytoskeleton ultrastructure and localization of microtubule-associated and spectrin-like proteins using quick-free, deep-etch, immunogold electron microscopy. J. Struct. Biol. 107 211-220. 

All cells contain an inner membrane skeleton of spectrin-like proteins. Red blood cell spectrin was the first member of the spectrin family described. The protein dystrophin present in skeletal muscle cells is a member of the spectrin family. Genetic defects in the dystrophin gene are responsible for Duchenne s and Becker s muscular dystrophies. 

Fluopicolide, a new Anti-oomycetes Fungicide with a New Mode of Action inducing Perturbation of a Spectrin-like Protein... 

Fluopicolide Effect on Spectrin-like Protein Distribution... 

Fig. 19.4. Kinetics of the fluopicolide effect on the distribution of the spectrin-like proteins in hyphae of P. infestans. Control cell (a). Hyphae treated with 10 ppm fluopicolide for 3 min (b), 10 min (c), 2 h (d) and 24 h (e).

Fig. 19.5. Kinetics of the fluopicolide effect on the distribution of the spectrin-like proteins in zoospores of P. irfestans. Control cell (a).

Fig. 19.5). Interestingly, this modification of the spectrin-like protein(s) cellular localization correlated very well with the phenotypic symptoms observed on zoospores. 

The action of anti-oomycete fungicides on spectrin-like protein(s) localization was compared with that of fluopicolide. Different times of treatment were tested, from 3 min to 24 h. Figure 19.6 illustrates the results obtained after 2 h of treatment. None of the fungicides tested (iprovalicarb, fenamidone, dimethomorph, metalaxyl and zoxamide) induced spectrin-like protein redistribution. Unlike for... 

Characterization of Spectrin-like Proteins in P. infistans by Bioanalysis... 

Fluopicolide-induced delocalization of spectrin-like proteins represents a new mode of action that is different to that of known anti-oomycete fungicides on the market. Spectrin-like proteins are poorly characterized in fungi and oomy-... 

Davison, M., and Critchley, D., 1988. o -Actinin and the DMD protein contain. spectrin-like repeats. C>//52 159-160. 

Xia, H., Winokur, S. T., Kuo, W. L., Altherr, M. R., and Bredt, D. S. (1997). Actinin-associated LIM protein Identification of a domain interaction between PDZ and spectrin-like repeat motifs./. Cell Biol. 139, 507-515. 

C. Hdtianu, L Bogdan, E Constantinescu, and M, Simionescu. Endothelial cells ex press a spectrin-like cyto skeletal protein. Circ. Res. 5ft605-7M (1986). 

C. Heltianit, I. Bogdan, E. Constandnescu, and M. Simionescu. Endothelial cells express a spectrin-like cytoakeletal protein. Clrc, Res. 58 605 (1986). 

Alam MR, Johnson RC, Darlington DN, Hand TA, Mains RE, Eipper BA (1997) Kalirin, a cytosolic protein with spectrin-like and GDP/ GTP exchange factor-like domains that interacts with peptidylgly-cine alpha-amidating monooxygenase, an integral membrane peptide-processing enzyme. J Biol Chem 272 12667-12675. 

Fig. 4. Structure of striated muscle costameres and the DPC. A single membrane-associated costamere from a portion of a striated muscle fiber is magnified above to show the components of the dystrophin-associated protein complex that are involved in linking desmin intermediate filaments (IFs) to the muscle cell membrane. Additional actin-associated proteins present at these sites (including vinculin, talin, spectrin, and ankyrin) are not shown here. In addition to components of the DPC, plectin has also been localized to costameres, and likely contributes to linking desmin IFs to actin-associated structures.

Fig. 2. Evolution of the spectrin superfamily. Rounded rectangles represent spectrin repeats. Shaded rectangles denote a-actinin-like repeats involved in dimerization, whereas unshaded rectangles represent repeats that were involved in duplication and/ or elongation events. The incomplete spectrin repeats involved in tetramer formation are proportionally represented depending on the number of repeat helices each protein contributes to the formation of a complete spectrin repeat. (Adapted from Dubreuil, 1991 Pascual et al., 1997.) A dystrophin/utrophin ancestor probably diverged from a-actinin at a relatively early stage and then underwent its own series of duplications and acquisitions of new motifs.

Indeed, homologous regions of all of the a-actinin protein domains can be found within the sequences of a- and /3-spectrin. For example, the amino and carboxy terminal regions of a-actinin resemble the N-terminus of /3-spectrin and the C-terminus of a-spectrin, respectively (Byers et al, 1989 Dubreuil et al, 1989). Phylogenetic analysis shows a common ancestor for the first repeat of a-actinin and the first repeat of /3-spectrin. Similarly, each of the remaining repeats in a-actinin (2—4) correspond to repeats 1 and 2 of /3-spectrin and repeats 19 and 20 of a-spectrin respectively (Fig. 2). This may have relevance for the function of these repeats in the dimerization of these proteins (Pascual et al, 1997). It is the similarity between these regions of a-actinin, the spectrins, and the simpler domain organization of a-actinin that have led to the hypothesis that these two protein families have evolved from an a-actinin-like precursor. 

Spectrin is a much more elongated protein compared to a-actinin due to the additional number of repeats. The additional repeats are more closely related to one another than repeats common to both a-actinin and spectrin. The spectrin repeat sequences are the most divergent in dystrophin and its homologue utrophin (Winder et al, 1995a), most likely reflecting an earlier divergent event when compared to spectrin (Pascual et al, 1997). 

Fig. 11. The structure of a-actinin and the two vertebrate Z-band lattices. (A) The ubiquitous protein a-actinin is an anti-parallel homodimer. Each 100 KDa monomer comprises four central spectrin repeats (SI to S4) an EF-hand domain and two calponin homology domains (CH) at the N-terminus. The EF-hand domains bind calcium in non-muscle cells. One a-actinin molecule binds two actin filaments via the calponin homology domains. a-Actinin binds titin via EF-hand domains. (B, C) The Z-band is the site where actin filaments from adjacent sarcomeres overlap in a tetragonal lattice and are crosslinked by a-actinin molecules. The polarity and origin of the actin filaments is indicated by U (up) and D (down). The appearance of the Z-band in cross-section is typically basketweave-like (B) or small square-like (G). The appearance is reported to transform between the two appearances depending on the state of the muscle.

The importance of the spleen in the pathophysiology of the hemolysis of HS has been substantiated. Two factors determine the selective destruction of the HS cells in the spleen (1) poor HS red cell deformability, which is a reflection of a decreased surface-to-volume ratio resulting from the loss of membrane and (2) the unique anatomy of the splenic vasculature, which acts as a microcirculation filter. As shown in Table 6-2, the underlying molecular basis of HS is heterogeneous, and the primary molecular lesion in HS is likely to involve several membrane proteins, including spectrin, ankyrin,... 

Trilaminar structure of the OHC s lateral wall. The three distinct layers are the SSC layer, the cortical lattice, and the plasma membrane. The SSCs are membranous sacs akin to the endoplasmic reticulum. The space between the SSC layer and the plasma membrane is occupied by the cortical lattice, which is composed of actin and spectrin filaments connected to the plasma membrane by an array of pillar-like structures. Protein particles embedded at high density in the plasma membrane are considered the motor proteins that drive the OHC s electromotility. Adapted from Figure 5-2 of Brownell and group (2001). Reprinted, with permission, from Annual Review of Biomedical Engineering, Volume 32001 by Annual Review www.annualreviews.org... 

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