Direct interaction of β-dystroglycan with F-actin

Chen, Yun‐Ju; Spence, Heather J.; Cameron, Jacqueline M.; Jess, Thomas J.; Ilsley, Jane L.; Winder, Steven J.

doi:10.1042/bj20030808

Cited by 67 publications

(57 citation statements)

References 40 publications

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“…Expression of DG recruits ezrin and induces a filopodia phenotype in REF52 cells. 17,18 Filopodia formation can be inhibited by the deletion of the entire β-DG cytoplasmic domain, by mutation of an ezrin binding site or by the co-expression of dominant-negative Cdc42. 17,18 Because the cytoplasmic domain of DG appeared to be able to alter the subcellular distribution of ezrin and Dbl and consequently the ability to form filopodia, and because depletion of DG by RNAi also reduced the ability to form filopodia, we examined the effect of the DG cytoplasmic domain on Cdc42-dependent filopodia formation in REF52 cells.…”

Section: Resultsmentioning

confidence: 99%

“…17,18 Filopodia formation can be inhibited by the deletion of the entire β-DG cytoplasmic domain, by mutation of an ezrin binding site or by the co-expression of dominant-negative Cdc42. 17,18 Because the cytoplasmic domain of DG appeared to be able to alter the subcellular distribution of ezrin and Dbl and consequently the ability to form filopodia, and because depletion of DG by RNAi also reduced the ability to form filopodia, we examined the effect of the DG cytoplasmic domain on Cdc42-dependent filopodia formation in REF52 cells. As reported previously, Cdc42 activity was necessary for the DG-induced filopodia phenotype and constitutively-active Cdc42 had a non-synergistic effect on DG-induced filopodia formation: an effect which could be completely blocked by deletion of the β-DG cytoplasmic domain.…”

Section: Resultsmentioning

confidence: 99%

“…We have previously shown that dystroglycan (DG) interacts with ERM family proteins 18 and that this interaction was necessary for the Cdc42-dependent induction of filopodia. 17 ERM proteins can interact with regulators of Rho family GTPases and target them to specific cellular locations including the cell periphery. In particular, ezrin and radixin have been shown to bind to Dbl, 21,22 a RhoGEF which shows exchange activity for Rho and Cdc42.…”

Section: Resultsmentioning

confidence: 99%

“…Cells were determined to have a filopodia phenotype if the cells had more than 30 filopodial protrusions over the whole surface. 17,18 Protein immunoblotting. Sub-confluent dishes of cells were washed twice with ice cold PBS and lysed with modified sample buffer (50 mM Tris pH 6.8, 1% SDS, 10% glycerol, 0.5 mM sodium fluoride, 1 mM PMSF, 10 mg/ml each of aprotinin, leupeptin and benzamidine and 100 mM sodium vanadate), for 5 min followed by sonication on ice.…”

Section: Constructsmentioning

confidence: 99%

“…8 We have shown recently that the cell adhesion receptor dystroglycan can induce filopodia formation in a Cdc42-and ezrindependent manner. 17,18 Dystroglycan has been most extensively characterised as a part of the dystrophin glycoprotein complex of skeletal muscle but also has roles in cell adhesion, cell polarity and morphogenesis in other tissues. 19 Ezrin radixin moesin (ERM) family proteins have previously been demonstrated to interact with components of the Rho GTPase signaling machinery, notably RhoGDI 20 and the GDP/GTP exchange factor (GEF) for Cdc42 and Rho: Dbl.…”

Section: Introductionmentioning

confidence: 99%

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Recruitment of Dbl by Ezrin and Dystroglycan Drives Membrane Proximal Cdc42 Activation and Filopodia Formation

Batchelor¹,

Higginson²,

Chen³

et al. 2007

Cell Cycle

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ACKnoWLEdgEmEntSWe are grateful to the following for supplies of antisera or plasmids, Art Alberts, P. Aspenstrom, Louise Anderson, Francis Barr and Sam Crouch, and to Kathryn Ayscough for comments on the manuscript. The work was funded by an MRC Career Establishment Grant to S.J.W., J.R.H. was in receipt of a BBSRC studentship and A.E. was supported by grants from the Italian Association for Cancer Research, Compagnia S. Paolo, and Ministero della Salute. ABStRACtDystroglycan is an essential laminin binding cell adhesion molecule, which is also an adaptor for several SH2 domain-containing signaling molecules and as a scaffold for the ERK-MAP kinase cascade. Loss of dystroglycan function is implicated in muscular dystrophies and the aetiology of epithelial cancers. We have previously demonstrated a role for dystroglycan and ezrin in the formation of filopodia structures. Here we demonstrate the existence of a dystroglycan:ezrin:Dbl complex that is targeted to the membrane by dystroglycan where it drives local Cdc42 activation and the formation of filopodia. Deletion of an ezrin binding site in dystroglycan prevented the association with ezrin and Dbl and the formation of filopodia. Furthermore, expression of the dystroglycan cytoplasmic domain alone had a dominant-negative effect on filopodia formation and Cdc42 activation by sequestering ezrin and Dbl away from the membrane. Depletion of dystroglycan inhibited Cdc42-induced filopodia formation. For the first time we also demonstrate co-localization of Cdc42 and dystroglycan at the tips of dynamic filopodia.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Constructsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Recruitment of Dbl by Ezrin and Dystroglycan Drives Membrane Proximal Cdc42 Activation and Filopodia Formation

Batchelor¹,

Higginson²,

Chen³

et al. 2007

Cell Cycle

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Giant scaffolding protein AHNAK1 interacts with β‐dystroglycan and controls motility and mechanical properties of schwann cells

Boxberg

Soares

Féréol

et al. 2014

Glia

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The profound morphofunctional changes that Schwann cells (SCs) undergo during their migration and elongation on axons, as well as during axon sorting, ensheathment, and myelination, require their close interaction with the surrounding laminin-rich basal lamina. In contrast to myelinating central nervous system glia, SCs strongly and constitutively express the giant scaffolding protein AHNAK1, localized essentially underneath the outer, abaxonal plasma membrane. Using electron microscopy, we show here that in the sciatic nerve of ahnak1(-) (/) (-) mice the ultrastructure of myelinated, and unmyelinated (Remak) fibers is affected. The major SC laminin receptor β-dystroglycan co-immunoprecipitates with AHNAK1 shows reduced expression in ahnak1(-) (/) (-) SCs, and is no longer detectable in Cajal bands on myelinated fibers in ahnak1(-) (/) (-) sciatic nerve. Reduced migration velocity in a scratch wound assay of purified ahnak1(-) (/) (-) primary SCs cultured on a laminin substrate indicated a function of AHNAK1 in SC motility. This was corroborated by atomic force microscopy measurements, which revealed a greater mechanical rigidity of shaft and leading tip of ahnak1(-) (/) (-) SC processes. Internodal lengths of large fibers are decreased in ahnak1(-) (/) (-) sciatic nerve, and longitudinal extension of myelin segments is even more strongly reduced after acute knockdown of AHNAK1 in SCs of developing sciatic nerve. Together, our results suggest that by interfering in the cross-talk between the transmembrane form of the laminin receptor dystroglycan and F-actin, AHNAK1 influences the cytoskeleton organization of SCs, and thus plays a role in the regulation of their morphology and motility and lastly, the myelination process.

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The extracellular matrix: Focus on oligodendrocyte biology and targeting CSPGs for remyelination therapies

Stephenson

Yong

2018

Glia

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The repair of myelin, termed remyelination, is a regenerative process that occurs within the central nervous system in conditions such as multiple sclerosis. Remyelination is enabled by oligodendrocytes that mature from oligodendrocyte precursor cells. Many factors influence the biology of oligodendrocytes and their capacity to reform myelin, and considerable evidence now implicates the extracellular matrix within the injured central nervous system as a major modifier of remyelination. Herein, we review current knowledge of components of the brain extracellular matrix that are beneficial or inhibitory for oligodendrocyte recruitment and maturation, and for their capacity to remyelinate where evidence exists. We highlight the detrimental roles of the chondroitin sulfate proteoglycans in remyelination and discuss approaches to alter the brain extracellular matrix for the wellbeing of oligodendrocytes and their capacity for myelin regeneration.

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Direct interaction of β-dystroglycan with F-actin

Cited by 67 publications

References 40 publications

Recruitment of Dbl by Ezrin and Dystroglycan Drives Membrane Proximal Cdc42 Activation and Filopodia Formation

Recruitment of Dbl by Ezrin and Dystroglycan Drives Membrane Proximal Cdc42 Activation and Filopodia Formation

Giant scaffolding protein AHNAK1 interacts with β‐dystroglycan and controls motility and mechanical properties of schwann cells

The extracellular matrix: Focus on oligodendrocyte biology and targeting CSPGs for remyelination therapies

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