Association of utrophin and multiple dystrophin short forms with the mammalian M(r) 58,000 dystrophin-associated protein (syntrophin).

Kramarcy, Neal R.; Vidal, Alexander; Froehner, Stanley C.; Sealock, Robert

doi:10.1016/s0021-9258(17)42023-0

Cited by 151 publications

(59 citation statements)

References 56 publications

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“…The main intracellular binding partners of ␤-DG are dystrophin and its homologue utrophin that directly interact with actin (23). Although dystrophin is restricted to myocytes and in kidney to collecting tubules and the glomerular mesangium (17), utrophin and short forms of dystrophin are widely expressed in nonmuscle cells, including podocytes (Figure 2) (24,25). Thus, podocytes are endowed with a set of components of a transmembrane DG complex that includes utrophin, ␣and ␤-DG, and laminin and proteoglycans in the GBM.…”

Section: Discussionmentioning

confidence: 99%

Glomerular Expression of Dystroglycans Is Reduced in Minimal Change Nephrosis But Not in Focal Segmental Glomerulosclerosis

Regele

Fillipovic

Langer

et al. 2000

Journal of the American Society of Nephrology

139

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Abstract. Extensive flattening of podocyte foot processes and increased permeability of the glomerular capillary filter are the major pathologic features of minimal change nephrosis (MCN) and focal segmental glomerulosclerosis (FSGS). Adhesion proteins anchor and stabilize podocytes on the glomerular basement membrane (GBM), and presumably are involved in the pathogenesis of foot process flattening. Thus far, α3 β1-integrin was localized to basal cell membrane domains. In this report, α- and β-dystroglycan (DG) were detected at precisely the same location by immunoelectron microscopy, and the presence of α- and β-DG chains was confirmed by immunoblotting on isolated human glomeruli. Because the major DG binding partners in the GBM (laminin, agrin, perlecan), and the intracellular dystrophin analogue utrophin are also present in glomeruli, it appears that podocytes adhere to the GBM via DG complexes, similar to muscle fibers in which actin is linked via dystrophin and DG to the extracellular matrix. As with muscle cells, it is therefore plausible that podocytes use precisely actin-guided DG complexes at their “soles” to actively govern the topography of GBM matrix proteins. Expression of the α/β-DG complex was reported to be reduced in muscular dystrophies, and therefore a search for similar pathologic alterations in archival kidney biopsies from patients with MCN (n = 16) and FSGS (n = 8) was conducted by quantitative immunoelectron microscopy. The density of α-DG on the podocyte's soles was significantly reduced to 25% in MCN, whereas it was not different in normal kidneys and FSGS. The expression of β-DG was reduced to >50% in MCN, and was slightly increased in FSGS. Levels of DG expression returned to normal in MCN after steroid treatment (n = 4). Expression of β1-integrin remained at normal levels in all conditions. These findings point to different potentially pathogenic mechanisms of foot process flattening in MCN and FSGS.

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Section: Discussionmentioning

confidence: 99%

Glomerular Expression of Dystroglycans Is Reduced in Minimal Change Nephrosis But Not in Focal Segmental Glomerulosclerosis

Regele

Fillipovic

Langer

et al. 2000

Journal of the American Society of Nephrology

139

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“…The size of myosin heavy chain (in kDa) is indicated. Dystrobrevin in muscle antibody 13H1 was raised against the Torpedo 87K protein (Carr et al, 1989) and detects multiple 87K/dystrobrevinreactive bands in different rat tissues (Kramarcy et al, 1994). Likewise, the polyclonal antibodies 308 and 433 detect αdystrobrevin-1, -2 and β-dystrobrevin in various mouse tissues (Blake et al, 1996(Blake et al, , 1998Peters et al, 1997a,b).…”

Section: Discussionmentioning

confidence: 99%

“…To determine the function of other dystrophin-related proteins at the synapse, we have focused our studies on αdystrobrevin (also known as 87K protein or A0). Dystrobrevin was originally identified in the Torpedo electric organ as a component of the postsynaptic membrane that co-purified with the AChRs, rapsyn, syntrophin and dystrophin (Carr et al, 1989;Butler et al, 1992;Wagner et al, 1993;Kramarcy et al, 1994;Dwyer and Froehner, 1995). Although α-dystrobrevin is closely associated with the AChRs, monoclonal antibodies raised against this protein label the sarcolemma as well as the NMJ of rodent skeletal muscle (Carr et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

“…Alternative splicing in cardiac and skeletal muscle generates α-dystrobrevin-1 and -2 transcripts that differ from their brain counterparts by the inclusion of the vr3 sequence preceding the coiled-coil encoding region (Blake et al, 1996;Ambrose et al, 1997). It has been established that α-dystrobrevin binds to syntrophin and dystrophin in different tissues (Kramarcy et al, 1994;Blake et al, 1996;Peters et al, 1997a). However, the antibodies used in these studies do not distinguish between αdystrobrevin-1 and -2, and the recently identified paralogue, βdystrobrevin (Peters et al, 1997b;Blake et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Characterisation of α-dystrobrevin in muscle

Nawrotzki

Loh

Rüegg

et al. 1998

Journal of Cell Science

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Dystrophin-related and associated proteins are important for the formation and maintenance of the mammalian neuromuscular junction. Initial studies in the electric organ of Torpedo californica showed that the dystrophin-related protein dystrobrevin (87K) co-purifies with the acetylcholine receptors and other postsynaptic proteins. Dystrobrevin is also a major phosphotyrosine-containing protein in the postsynaptic membrane. Since inhibitors of tyrosine protein phosphorylation block acetylcholine receptor clustering in cultured muscle cells, we examined the role of alpha-dystrobrevin during synapse formation and in response to agrin. Using specific antibodies, we show that C2 myoblasts and early myotubes only produce alpha-dystrobrevin-1, the mammalian orthologue of Torpedo dystrobrevin, whereas mature skeletal muscle expresses three distinct alpha-dystrobrevin isoforms. In myotubes, alpha-dystrobrevin-1 is found on the cell surface and also in acetylcholine receptor-rich domains. Following agrin stimulation, alpha-dystrobrevin-1 becomes re-localised beneath the cell surface into macroclusters that contain acetylcholine receptors and another dystrophin-related protein, utrophin. This redistribution is not associated with tyrosine phosphorylation of alpha-dystrobrevin-1 by agrin. Furthermore, we show that alpha-dystrobrevin-1 is associated with both utrophin in C2 cells and dystrophin in mature skeletal muscle. Thus alpha-dystrobrevin-1 is a component of two protein complexes in muscle, one with utrophin at the neuromuscular junction and the other with dystrophin at the sarcolemma. These results indicate that alpha-dystrobrevin-1 is not involved in the phosphorylation-dependent, early stages of receptor clustering, but rather in the stabilisation and maturation of clusters, possibly via an interaction with utrophin.

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“…28) ενώ το πολύ ακραίο τµήµα του καρβοξυτελικού άκρου της δυστροφίνης συνδέεται άµεσα µε µία οµάδα κυτταροπλασµατικών περιφερικών πρωτεϊνών γνωστών σαν συντροφίνες (Adams et al, 1993(Adams et al, , 1995Ahn et al, 1994a,b;Froehner et al, 1987;Piluso et al, 2000). Παρόµοια αλληλεπίδραση έχει δειχθεί για την ουτροφίνη, µία συγγενική πρωτεϊνη µε την δυστροφίνη που κωδικοποιείται απο αυτοσωµικό γονίδιο (Kramarcy et al, 1994) καθώς και για µερικές ισοµορφές της δυστροµπρεβίνης (Peters et al, 1997a,b). Η λειτουργία του συµπλόκου DAPC είναι πολύ περισσότερο κατανοητή στα µυϊκά κύτταρα, όπου παίζει κεντρικό ρόλο στη σταθεροποίηση του µυός καθώς συστέλλεται και χαλαρώνει (Blake & Davies, 1997).…”

Section: 22unclassified

Μοριακή ανάλυση και δράση του μορίου BM88 και πρώτη περιγραφή ενός νέου νευροειδικού γονιδίου (mc7)

Boutou¹,

Μπούτου²

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Μο ορ ρι ια ακ κή ή α αν νά άλ λυ υσ ση η κ κα αι ι δ δρ ρά άσ ση η τ το ου υ μ μο ορ ρί ίο ου υ Β ΒΜ Μ8 88 8 κ κα αι ι π πρ ρώ ώτ τη η π πε ερ ρι ιγ γρ ρα αφ φή ή ε εν νό ός ς ν νέ έο ου υ ν νε ευ υρ ρο οε ει ιδ δι ικ κο ού ύ γ γο ον νι ιδ δί ίο ου υ ( (m mc c7 7) ) Δ Δι ιδ δα ακ κτ το ορ ρι ικ κή ή Δ Δι ια ατ τρ ρι ιβ βή ή Ε Ευ υφ φρ ρο οσ σύ ύν νη η Μ Μπ πο ού ύτ το ου υ Β Βι ιο ολ λό όγ γο ος ς

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Association of utrophin and multiple dystrophin short forms with the mammalian M(r) 58,000 dystrophin-associated protein (syntrophin).

Cited by 151 publications

References 56 publications

Glomerular Expression of Dystroglycans Is Reduced in Minimal Change Nephrosis But Not in Focal Segmental Glomerulosclerosis

Glomerular Expression of Dystroglycans Is Reduced in Minimal Change Nephrosis But Not in Focal Segmental Glomerulosclerosis

Characterisation of α-dystrobrevin in muscle

Μοριακή ανάλυση και δράση του μορίου BM88 και πρώτη περιγραφή ενός νέου νευροειδικού γονιδίου (mc7)

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