Dystroglycan distribution in adult mouse brain: a light and electron microscopy study

Zaccaria, Maria Letizia; Tommaso, Francesca Di; Brancaccio, Andrea; Paggi, Paola; Petrucci, Tamara C.

doi:10.1016/s0306-4522(01)00092-6

Cited by 157 publications

(149 citation statements)

References 54 publications

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“…The failure to detect α-DG in the DG-overexpressing derivatives of the MCF7 cells cannot simply be a consequence of an altered glycosylation of the α-DG subunit since it was also undetectable using a polyclonal antibody which specifically recognizes and binds the N-terminal region of the α-DG core protein. 23 We previously demonstrated that reduction or loss of α-DG expression in most breast cancer cell lines is associated with accumulation of a low molecular weight form of the β-DG subunit 10 which has been shown to be a product of a proteolytic processing of the extracellular domain of β-DG likely due to a membrane-associated matrix metalloproteinase (MMP) activity. 10,13 The MCF7 cells have been reported to express the MMP15 and MMP16 enzymes 36 which might play a role in the loss of α-DG expression.…”

Section: Discussionmentioning

confidence: 99%

“…11 The polyclonal antibody to α-DG was raised in rabbits immunised with a recombinant fragment spanning the N-terminal region of mouse α-DG (30-315) 22 and was previously shown to be able to detect α-DG protein in western blot analysis. 23 Semiquantitative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Analysis. Total RNA was extracted from exponentially growing cultures of each cell line using the RNeasy Mini kit (Qiagen, Hilden, Germany), in accordance with the manufacturer's instructions and the RNA samples were reverse transcribed using the One-step RT-PCR kit (Qiagen).…”

Section: Methodsmentioning

confidence: 99%

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Increased expression of dystroglycan inhibits the growth and tumorigenicity of human mammary epithelial cells

Sgambato¹,

Camerini²,

Faraglia³

et al. 2004

Cancer Biology & Therapy

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Dystroglycan (DG) is an adhesion molecule formed by two subunits, α (extracellular) and β (transmembrane) DG, which are codified by a single gene and form a continuous link from the extracellular matrix to the intracellular cytoskeleton. Reduction or loss of expression of DG has been observed in human cancer cell lines and primary tumors and has been suggested to promote tumor development and invasiveness.In this study, the human breast epithelial non-tumorigenic MCF10F and the breast cancer MCF7 cell lines were engineered to stably express an exogenous DG cDNA and the effects on the phenotype of both cell lines were evaluated. The MCF10F transfected cells displayed an increased expression of both DG subunits which was associated with inhibition of the anchorage-dependent growth, accumulation of cells in the G 0 /G 1 phase of the cell cycle and increased adhesion to a substratum. The MCF7 transfected cells were unable to restore α-DG despite an increased expression of the β-DG subunit. Anchoragedependent and independent growth and the in vivo tumorigenicity were reduced in these derivatives that also displayed a reduced adhesion to a substratum and were shown to release α-DG in the culture medium.These findings confirm and extend previous evidence that transformation of mammary epithelial cells is associated with loss of their ability to retain α-DG on the cell membrane. Moreover, they indicate that DG is involved in cell functions other than cell adhesion to the extracellular matrix, and that its loss of function might predispose to tumor progression by compromising regulatory controls over cell growth and proliferation.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Increased expression of dystroglycan inhibits the growth and tumorigenicity of human mammary epithelial cells

Sgambato¹,

Camerini²,

Faraglia³

et al. 2004

Cancer Biology & Therapy

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“…The role of alpha-DG in developing brain and in neuronal migration has been studied in animals models 11,18,158,159,162,163 . Zaccaria et al 162 found that in adult mice alpha-DG is expressed in neurons of the cerebral cortex, hippocampus, olfactory bulb, basal ganglia, thalamus, hypothalamus, brainstem and cerebellum; in addition the astrocytes and their endfeet around blood vessels and the endothelial cells at the blood-brain barrier, also expressed DG.…”

Section: Disorders Of Glycosylation Of Alphadg (Alpha-dystroglycanopamentioning

confidence: 99%

“…Zaccaria et al 162 found that in adult mice alpha-DG is expressed in neurons of the cerebral cortex, hippocampus, olfactory bulb, basal ganglia, thalamus, hypothalamus, brainstem and cerebellum; in addition the astrocytes and their endfeet around blood vessels and the endothelial cells at the blood-brain barrier, also expressed DG. During CNs development, alpha-DG is expressed in the ventricular zone and in basement membranes, therefore participating in neuronal proliferation, in the constitution of the meningeal layer and in migration process as the radial glia is attached to the pial basement membrane 158 .…”

Section: Disorders Of Glycosylation Of Alphadg (Alpha-dystroglycanopamentioning

confidence: 99%

Congenital muscular dystrophy. Part II: a review of pathogenesis and therapeutic perspectives

Reed

2009

Arq. Neuro-Psiquiatr.

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-The congenital muscular dystrophies (CMDs) are a group of genetically and clinically heterogeneous hereditary myopathies with preferentially autosomal recessive inheritance, that are characterized by congenital hypotonia, delayed motor development and early onset of progressive muscle weakness associated with dystrophic pattern on muscle biopsy. The clinical course is broadly variable and can comprise the involvement of the brain and eyes. From 1994, a great development in the knowledge of the molecular basis has occurred and the classification of CMDs has to be continuously up dated. In the last number of this journal, we presented the main clinical and diagnostic data concerning the different subtypes of CMD. In this second part of the review, we analyse the main reports from the literature concerning the pathogenesis and the therapeutic perspectives of the most common subtypes of CMD: MDC1A with merosin deficiency, collagen VI related CMDs (Ullrich and Bethlem), CMDs with abnormal glycosylation of alpha-dystroglycan (Fukuyama CMD, Muscleeye-brain disease, Walker Warburg syndrome, MDC1C, MDC1D), and rigid spine syndrome, another much rare subtype of CMDs not related with the dystrophin/glycoproteins/extracellular matrix complex.Key WorDs: congenital muscular dystrophy, MDC1A, collagen VI related disorders, glycosylation of alphadystroglycan, Fukuyama DMC, muscle-eye-brain (MeB) disease, Walker-Warburg syndrome, rigid spine syndrome. distrofia muscular congênita. parte ii: revisão da patogênese e perspectivas terapêuticas resumo -As distrofias musculares congênitas (DMCs) são miopatias hereditárias geralmente, porém não exclusivamente, de herança autossômica recessiva, que apresentam grande heterogeneidade genética e clínica. são caracterizadas por hipotonia muscular congênita, atraso do desenvolvimento motor e fraqueza muscular de início precoce associada a padrão distrófico na biópsia muscular. o quadro clínico, de gravidade variável, pode também incluir anormalidades oculares e do sistema nervoso central. A partir de 1994, os conhecimentos sobre genética e biologia molecular das DMCs progrediram rapidamente, sendo a classificação continuamente atualizada. os aspectos clínicos e diagnósticos dos principais subtipos de DMC foram apresentados no número anterior deste periódico, como primeira parte desta revisão. Nesta segunda parte apresentaremos os principais mecanismos patogênicos e as perspectivas terapêuticas dos subtipos mais comuns de DMC: DMC tipo 1A com deficiência de merosina, DMCs relacionadas com alterações do colágeno VI (Ullrich e Bethlem), e DMCs com anormalidades de glicosilação da alfa-distroglicana (DMC Fukuyama, DMC "Muscle-eye-brain" ou MeB, síndrome de Walker Warburg, DMC tipo 1C, DMC tipo 1D). A DMC com espinha rígida, mais rara e não relacionada com alterações do complexo distrofina-glicoproteínas associadas-matriz extracelular também será abordada quanto aos mesmos aspectos patogênicos e terapêuticos.PAlAVrAs-ChAVes: distrofia muscular congênita, merosina, colágeno VI, glicosila...

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“…Additionally, the parenchymal basement membrane is linked to the astrocytic endfoot membrane through interactions with ECM components present on both sides [51,52]. Dystroglycan, which is exclusively expressed on the astrocytic endfoot membrane [53,64] participates in these interactions, and it is known to be a substrate of MMP-2 and -9 [1]. In light of these findings, the delay in leukocyte extravasation is likely the result of increased barriers that serve to protect endothelial cells of parenchymal vessels of the necessary signals for leukocyte diapedesis which includes activation of functional MMPs.…”

Section: Discussionmentioning

confidence: 99%

Multiple expression of matrix metalloproteinases in murine neurocysticercosis: Implications for leukocyte migration through multiple central nervous system barriers

Alvarez

Teale

2008

Brain Research

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During the course of murine neurocysticercosis (NCC), disruption of the unique protective barriers in the central nervous system (CNS) is evidenced by extravasation of leukocytes. This process varies according to the anatomical sites and diverse vascular beds analyzed. To examine mechanisms involved in the observed differences, the expression and activity of eight matrix metalloproteinases (MMPs) were analyzed in a murine model of NCC. The mRNA expression of the MMPs studied was upregulated as a result of infection, and active MMPs were mainly detected in leukocytes migrating into the brain. Polarized expression and gelatinolytic activity of several MMPs were identified in immune cells extravasating pial vessels as early as 1 day post infection. In contrast, leukocytes expressing active MMPs and extravasating parenchymal vessels were not observed until 5 weeks post infection. In ventricular areas, most of the MMP activity was detected in leukocytes traversing the ependyma from leptomeningeal infiltrates. In addition, immune cells continued to express active MMPs after exiting vessels suggesting that enzymatic activity of MMPs is not just required for diapedesis. These results correlate with our previous studies showing differential kinetics in the disruption of the CNS barriers upon infection and help document the important role of MMPs during leukocyte infiltration and inflammation.

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Dystroglycan distribution in adult mouse brain: a light and electron microscopy study

Cited by 157 publications

References 54 publications

Increased expression of dystroglycan inhibits the growth and tumorigenicity of human mammary epithelial cells

Increased expression of dystroglycan inhibits the growth and tumorigenicity of human mammary epithelial cells

Congenital muscular dystrophy. Part II: a review of pathogenesis and therapeutic perspectives

Multiple expression of matrix metalloproteinases in murine neurocysticercosis: Implications for leukocyte migration through multiple central nervous system barriers

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