Evidence for Transmembrane Anchoring of Extracellular Matrix at Acetylcholine Receptor Clusters

Dmytrenko, George M.; Bloch, Robert J.

doi:10.1006/excr.1993.1153

Cited by 8 publications

(4 citation statements)

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“…Many of the identified proteins presented here have been described to be associated with cell signaling compounds. The clustering of AChRs depends on the presence of a spectrin-based membrane skeleton that anchors extracellular matrix molecules to synaptic regions [45,46]. Moreover, 14-3-3, PLP and syntaxins have been reported to regulate the expression, formation and function of AChRs in muscle and brain [47][48][49].…”

Section: Discussionmentioning

confidence: 99%

Identification of proteins with high affinity for refolded and native PrPC

Petrakis

Sklaviadis

2006

Proteomics

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PrPC, the cellular prion protein, is widely expressed in most tissues, including brain, muscle and the gastrointestinal tract, but its physiological role remains unclear. During propagation of transmissible spongiform encephalopathies (TSEs), prion protein is converted to the pathological isoform, PrPSc, in a process believed to be mediated by as-yet-unknown host factors. The identification of proteins associated with PrP may provide information about the biology of prions and the pathogenesis of TSEs. In the present work, we report proteins identified from brain tissue based on their ability to bind to recombinant PrP (recPrP) or form multimolecular complexes with native PrPC in the presence of cross-linkers. Immobilized his-tagged recPrP was used as an affinity matrix to isolate PrP-interacting proteins from brain homogenates of normal individuals. In parallel, PrPC-associated proteins were characterized by cross-linking and co-immunoprecipitation assays. The unknown molecules were identified by MS and the results of LC-MS/MS analysis were subsequently verified by Western blot. Both techniques resulted in identification of proteins participating in the formation of cytoskeleton and signal transduction, further supporting the hypothesis that PrP is involved in the organization and function of receptors throughout the nervous system.

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Section: Discussionmentioning

confidence: 99%

Identification of proteins with high affinity for refolded and native PrPC

Petrakis

Sklaviadis

2006

Proteomics

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“…The communication between the extracellular matrix (ECM) and the actin cytoskeleton (especially the α‐actinin component) indicates a direct involvement of basal lamina molecules such as fibronectin, collagen IV, or laminin in cytoskeletal handling of the plasma membrane nicotinic receptor [33]. This could also apply to the Y2 receptor.…”

Section: Discussionmentioning

confidence: 99%

A pool of Y2 neuropeptide Y receptors activated by modifiers of membrane sulfhydryl or cholesterol balance

Parker

Kane

et al. 2002

European Journal of Biochemistry

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The cloned guinea-pig Y2 neuropeptide Y (NPY) receptors expressed in Chinese hamster ovary (CHO) cells, as well as the Y2 receptors natively expressed in rat forebrain, are distributed in two populations. A smaller population that is readily accessed by agonist peptides on the surface of intact cells constitutes less than 30% of Y2 receptors detected in particulates after cell homogenization. A much larger fraction of cell surface Y2 sites can be activated by sulfhydryl modifiers. A fast and large activation of these masked or cryptic sites could be obtained with membrane-permeating, vicinal cysteine-bridging arsenical phenylarsine oxide. A lower activation is effected by N-ethylmaleimide, an alkylator that slowly penetrates lipid bilayers. The restricted-access alkylator, 2-[(trimethylammonium)ethyl]methanethiosulfonate, was not effective in unmasking these sites. Some of the hidden cell surface Y2 sites could be activated by polyene filipin III through complexing of membrane cholesterol. The results are consistent with the presence of a large Y2 reserve in a compartment that can be accessed by alteration of sulfhydryl balance or fluidity of the cell membrane, and by treatments that affect the anchoring and aggregation of membrane proteins.Keywords: receptor sequestration; receptor reserve; receptor signaling; receptor masking.Synaptic discharge of many neurotransmitters produces concentrations of these receptor agonists that saturate the respective binding sites, with a potential for prolonged and excessive signaling. With receptors characterized by high binding affinities, which represent a large fraction of rhodopsin-related neurotransmitter receptors, it may not be possible to adequately constrain the signaling by dissociation of the agonist. For neuropeptide receptors, a paracrine regulation via secretion of specific peptidases would meet large difficulties in both the selectivity and the economy of action. Scavenging by cell membrane-resident ectoproteinases by way of in situ encounters with extracellular agonists may not satisfy the clearance needs created by agonist discharge. A much more selective (and potentially quicker) regulation could be provided by sequestration or internalization of the receptor-ligand complex and further intramembrane or intracellular processing (reviewed in [1,2]). This could be accomplished by recycling sequestration (e.g. the m1 muscarinic receptor [3]), by recycling internalization (e.g. the m2 muscarinic receptor [4] or the neuropeptide Y (NPY) Y1 receptor [5]), and by lysosome-linked disposing internalization (e.g. the endothelin-B receptor [6]), all possibly enacted in relation to the prevailing levels of the respective agonists and the extent of preservation of the respective receptor molecules. Among neuropeptide transmitters, large levels of NPY are present in many areas of the forebrain [7], enabling an important regulation of feeding [8]. The forebrain NPY receptors include all principal Y receptor types [9], with Y1 and Y2 receptors detected at largest levels [10]....

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“…Other reports (5,16,20,21) have identified the nAChR as the initial rabies virus cell target. Interestingly, extracellular matrix molecules, including fibronectin, codistribute with nAChR clusters (12,13). Thus, fibronectin should be considered as part and parcel of the VHSV and other fish rhabdovirus cell receptor complexes, playing a role in the initial binding step, which is probably followed by a secondary binding, allowing the virus to enter into the cell by fusion or by endocytosis (19).…”

Section: Discussionmentioning

confidence: 99%

Fish Rhabdovirus Cell Entry Is Mediated by Fibronectin

Béarzotti

Delmas

Lamoureux

et al. 1999

J Virol

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Three monoclonal antibodies (MAbs) generated against rainbow trout gonad cells (RTG-2) have been selected for their ability to protect cells from the viral hemorrhagic septicemia virus (VHSV) infection, a salmonid rhabdovirus. Protection from infection was restricted to the salmonid-derived cell lines indicating species specificity of the blocking MAbs. Surprisingly, the blocking activity of these MAbs was also effective against other nonantigenically related fish rhabdoviruses. Indirect immunofluorescence and immunoelectron microscopy observations demonstrated that the three MAbs were all directed against an abundant cell plasma membrane component, and immunoprecipitation studies indicated that the target consisted of a heterodimeric complex with molecular masses of 200 and 44 kDa. Biochemical data provided the following evidence that fibronectin is part of this complex and that it could represent the main receptor for fish rhabdoviruses. (i) An antiserum generated against the 200-kDa protein reacted against the recombinant rainbow trout fibronectin expressed in Escherichia coli. (ii) The purified rainbow trout fibronectin was able to bind specifically to VHSV. To our knowledge, this is the first identification of a cellular component acting as a primary receptor for a virus replicating in lower vertebrates and, more interestingly, for viruses belonging to theRhabdoviridae family.

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Evidence for Transmembrane Anchoring of Extracellular Matrix at Acetylcholine Receptor Clusters

Cited by 8 publications

References 0 publications

Identification of proteins with high affinity for refolded and native PrPC

Identification of proteins with high affinity for refolded and native PrPC

A pool of Y2 neuropeptide Y receptors activated by modifiers of membrane sulfhydryl or cholesterol balance

Fish Rhabdovirus Cell Entry Is Mediated by Fibronectin

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