Cell type‐specific association between two types of spectrin and two types of intermediate filaments

Langley, Robert C.; Cohen, Carl M.

doi:10.1002/cm.970080208

Cited by 34 publications

(7 citation statements)

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“…We found that βII spectrin immunoreactivity was detected like 4.1B all along the internodal axolemma in sciatic nerve, whereas this cortical enrichment was altered in the absence of 4.1B. βII spectrin can associate with neurofilaments and may promote the association of intermediate filaments with the plasma membrane and contribute to the organization of neurofilaments [47]–[49]. Since neurofilaments control axonal radial growth with their subunit composition playing a crucial role in determining normal axonal calibers [50], 4.1B might control axonal caliber by controlling intermediate filaments organization through its association with βII spectrin.…”

Section: Discussionmentioning

confidence: 77%

Protein 4.1B Contributes to the Organization of Peripheral Myelinated Axons

et al. 2011

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Neurons are characterized by extremely long axons. This exceptional cell shape is likely to depend on multiple factors including interactions between the cytoskeleton and membrane proteins. In many cell types, members of the protein 4.1 family play an important role in tethering the cortical actin-spectrin cytoskeleton to the plasma membrane. Protein 4.1B is localized in myelinated axons, enriched in paranodal and juxtaparanodal regions, and also all along the internodes, but not at nodes of Ranvier where are localized the voltage-dependent sodium channels responsible for action potential propagation. To shed light on the role of protein 4.1B in the general organization of myelinated peripheral axons, we studied 4.1B knockout mice. These mice displayed a mildly impaired gait and motility. Whereas nodes were unaffected, the distribution of Caspr/paranodin, which anchors 4.1B to the membrane, was disorganized in paranodal regions and its levels were decreased. In juxtaparanodes, the enrichment of Caspr2, which also interacts with 4.1B, and of the associated TAG-1 and Kv1.1, was absent in mutant mice, whereas their levels were unaltered. Ultrastructural abnormalities were observed both at paranodes and juxtaparanodes. Axon calibers were slightly diminished in phrenic nerves and preterminal motor axons were dysmorphic in skeletal muscle. βII spectrin enrichment was decreased along the axolemma. Electrophysiological recordings at 3 post-natal weeks showed the occurrence of spontaneous and evoked repetitive activity indicating neuronal hyperexcitability, without change in conduction velocity. Thus, our results show that in myelinated axons 4.1B contributes to the stabilization of membrane proteins at paranodes, to the clustering of juxtaparanodal proteins, and to the regulation of the internodal axon caliber.

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Section: Discussionmentioning

confidence: 77%

Protein 4.1B Contributes to the Organization of Peripheral Myelinated Axons

et al. 2011

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“…Several candidate proteins that may be involved in the interaction with phospho-ser52 K18 include desmoplakin (DP), fodrin, or other cell surface associated proteins such as integrins. Although to our knowledge a fodrin-keratin interaction has not been described, such an interaction would not be surprising given the polarized distribution of fodrin in epithelial cells (reviewed by Bennett and Gilligan, 1993), and the described association between fodrin and other IF proteins including vimentin (Mangeat and Burridge, 1984), NF (Frappier et al, 1987;Langley and Cohen, 1987), and peripherin (Takemura et al, 1993). In addition, cell surface associated receptors could also potentially interact with the phospho-ser52 K18.…”

Section: Potential Implications For the Polarity Of Distribution Of Pmentioning

confidence: 86%

Dynamics of human keratin 18 phosphorylation: polarized distribution of phosphorylated keratins in simple epithelial tissues.

Liao

Lowthert

et al. 1995

The Journal of Cell Biology

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Abstract. Phosphorylation of keratin polypeptides 8 and 18 (K8/18) and other intermediate filament proteins results in their reorganization in vitro and in vivo. In order to study functional aspects of human K18 phosphorylation, we generated and purified a polyclonal antibody (termed 3055) that specifically recognizes a major phosphorylation site (ser52) of human K18 but not dephosphorylated K18 or a ser52~ala K18 mutant. Pulse-chase experiments followed by immunoprecipitation and peptide mapping of in vivo 32po 4-labeled K8/18 indicated that the overall phosphorylation turnover rate is faster for K18 versus K8, and that ser52 of K18 is a highly dynamic phosphorylation site. Isoelectric focusing of 32po 4 labeled K18 followed by immunoblotting with 3055 showed that the major phosphorylated K18 species contain ser52 phosphorylation but that some K18 molecules exist that are preferentially phosphorylated on K18 sites other than ser52. Immunoblotting of total cell lysates obtained from cells at different stages of the cell cycle showed that ser52 phosphorylation increases three to fourfold during the S and G2/M phases of the cell cycle. Immunofluorescence staining of cells at different stages of mitosis, using 3055 or other antibodies that recognize the total keratin pool, resulted in preferential binding of the 3055 antibody to the reorganized keratin fraction. Staining of human tissues or tissues from transgenic mice that express human K18 showed that the phospho-ser52 K18 species are located preferentially in the basolateral and apical domains in the liver and pancreas, respectively, but no preferential localization was noted in other simple epithelial organs examined. Our results support a model whereby phosphorylated intermediate filaments are localized in specific cellular domains depending on the tissue type and sites(s) of phosphorylation. In addition, ser52 of human K18 is a highly dynamic phosphorylation site that undergoes modulation during the S and G2/M phases of the cell cycle in association with filament reorganization.

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“…This suggests that, unlike desmin, which not only interacts with the sarcolemma at Z line domains but also surrounds the Z disks throughout the myoplasm, cytokeratins may interact preferentially with the sarcolemma. Because other members of the IF superfamily can bind to ␤-spectrins (Langley and Cohen, 1987;Frappier et al, 1992aFrappier et al, , 1992bMacioce et al, 1999), cytokeratin-sarcolemmal interactions may even be mediated Figure 9. Model of the sarcolemmal membrane skeleton and its relationship to desmin and cytokeratin.…”

Section: Discussionmentioning

confidence: 99%

“…Although it is tempting to speculate that desmin IFs anchor to ␣-fodrin at the sarcolemma at Z line domains, binding of desmin to ␣ subunits of the spectrin superfamily has yet to be reported. Desmin and other IF proteins bind to spectrin and to ankyrin (Georgatos and Blobel, 1987;Langley and Cohen, 1987;Frappier et al, 1991Frappier et al, , 1992Macioce et al, 1999), however, so anchoring of desmin IFs to the sarcolemma may be mediated by the ␣␤-spectrin heteromers and ankyrin that are present at Z line domains (Porter et al, 1997;Williams and Bloch, 1999b;Williams et al, 2001; see Figure 9). …”

Section: Discussionmentioning

confidence: 99%

Sarcolemmal Organization in Skeletal Muscle Lacking Desmin: Evidence for Cytokeratins Associated with the Membrane Skeleton at Costameres

O’Neill

Williams

Resneck

et al. 2002

MBoC

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The sarcolemma of fast-twitch muscle is organized into "costameres," structures that are oriented transversely, over the Z and M lines of nearby myofibrils, and longitudinally, to form a rectilinear lattice. Here we examine the role of desmin, the major intermediate filament protein of muscle in organizing costameres. In control mouse muscle, desmin is enriched at the sarcolemmal domains that lie over nearby Z lines and that also contain ␤-spectrin. In tibialis anterior muscle from mice lacking desmin due to homologous recombination, most costameres are lost. In myofibers from desmin Ϫ/Ϫ quadriceps, by contrast, most costameric structures are stable. Alternatively, Z line domains may be lost, whereas domains oriented longitudinally or lying over M lines are retained. Experiments with pan-specific antibodies to intermediate filament proteins and to cytokeratins suggest that control and desmin Ϫ/Ϫ muscles express similar levels of cytokeratins. Cytokeratins concentrate at the sarcolemma at all three domains of costameres when the latter are retained in desmin Ϫ/Ϫ muscle and redistribute with ␤-spectrin at the sarcolemma when costameres are lost. Our results suggest that desmin associates with and selectively stabilizes the Z line domains of costameres, but that cytokeratins associate with all three domains of costameres, even in the absence of desmin. INTRODUCTIONDuchenne Muscular Dystrophy and related muscular dystrophies are caused by the mutation or loss of dystrophin and dystrophin-associated proteins (Campbell, 1995;Bonnemann et al., 1996;Straub and Campbell, 1997;Ozawa et al., 1998), respectively, but the functions of these proteins in healthy skeletal muscle are still poorly understood. Dystrophin, which is a member of the spectrin superfamily of membrane skeletal proteins (Davison and Critchley, 1988;Koenig et al., 1988;Dhermy, 1991;Ahn and Kunkel, 1993), accumulates in healthy muscle on the cytoplasmic face of the sarcolemma in linear structures that are oriented both longitudinally and transversely (Masuda et al., 1992;Minetti et al., 1992;Porter et al., 1992;Straub et al., 1992;Williams and Bloch, 1999b). The transverse structures, which lie at the sarcolemma over the Z and M lines of nearby myofibrils, are organized in a rib-like pattern and so are referred to as "costameres" (Pardo et al., 1983a). We also use this term to include the longitudinal elements, which, with the transverse domains, form a lattice-like network that underlies most of the skeletal muscle sarcolemma. All three costameric domains are enriched in dystrophin (Porter et al., 1992). We have found that, in the absence of dystrophin, the longitudinal and M line domains of costameres are more susceptible to disruption in Duchenne muscle and in muscle from the mdx mouse (Porter et al., 1992;Williams and Bloch, 1999b; see also Ehmer et al., 1997), suggesting that dystrophin functions more to stabilize these sarcolemmal domains than the domains that overlie Z lines. These studies also suggest that other structures associated with the sarco...

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Cell type‐specific association between two types of spectrin and two types of intermediate filaments

Cited by 34 publications

References 37 publications

Protein 4.1B Contributes to the Organization of Peripheral Myelinated Axons

Protein 4.1B Contributes to the Organization of Peripheral Myelinated Axons

Dynamics of human keratin 18 phosphorylation: polarized distribution of phosphorylated keratins in simple epithelial tissues.

Sarcolemmal Organization in Skeletal Muscle Lacking Desmin: Evidence for Cytokeratins Associated with the Membrane Skeleton at Costameres

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