The rotational diffusion of the acetylcholine receptor in Torpeda marmorata membrane fragments studied with a spin-labelled alpha-toxin: importance of the 43 000 protein(s).

Rousselet, Annie; Cartaud, Jean; Devaux, PF; Changeux, Jean‐Pierre

doi:10.1002/j.1460-2075.1982.tb01188.x

Cited by 88 publications

(37 citation statements)

References 36 publications

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“…The binding of anti-AcChoR antibodies to the membrane-bound receptor increases 4-fold after alkaline extraction of the membranes (unpublished data). Finally, the rotational mobility of the membrane-bound receptor is greatly enhanced by alkaline extraction (19,20). These results suggest that the Mr 43,000 protein may interact with the AcChoR in the membrane.…”

mentioning

confidence: 83%

Immunofluorescence localization at the mammalian neuromuscular junction of the Mr 43,000 protein of Torpedo postsynaptic membranes.

Froehner

Gulbrandsen

Hyman

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

133

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Highly purified cholinergic postsynaptic membranes from Torpedo electric tissue contain, in addition to the acetylcholine receptor (AcChoR), major proteins ofMr 43,000 and Mr -90,000 and minor proteins that can be removed from the membranes by alkaline treatment. We have prepared an antiserum to these alkaline-extractable proteins that reacts with the Mr 43,000 protein but not with any of the other major membrane nroteins, including the AcChoR subunits. Immunofluorescent staining of sections of Torpedo electric tissue shows that this antiserum binds to the innervated but not the uninnervated surface of the electrocytes. In rat diaphragm muscle, the antigens recognized by this antiserum are highly concentrated at the synapse.

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mentioning

confidence: 83%

Immunofluorescence localization at the mammalian neuromuscular junction of the Mr 43,000 protein of Torpedo postsynaptic membranes.

Froehner

Gulbrandsen

Hyman

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

133

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“…For example, extraction of rapsyn from clusters on rat myotubes or from Torpedo electrocytes increases AChR mobility in the membrane (38,39). Furthermore, rapsyn mediates interaction of AChRs with the dystrophin/utrophin glycoprotein complex, which binds to F-actin (15).…”

Section: Agrin Increases the Interaction Of Rapsyn With Surface Achrsmentioning

confidence: 99%

Agrin Regulates Rapsyn Interaction with Surface Acetylcholine Receptors, and This Underlies Cytoskeletal Anchoring and Clustering

Moransard¹,

Borges²,

Willmann³

et al. 2003

Journal of Biological Chemistry

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The acetylcholine receptor (AChR)-associated protein rapsyn is essential for neuromuscular synapse formation and clustering of AChRs, but its mode of action remains unclear. We have investigated whether agrin, a key nerve-derived synaptogenic factor, influences rapsyn-AChR interactions and how this affects clustering and cytoskeletal linkage of AChRs. By precipitating AChRs and probing for associated rapsyn, we found that in denervated diaphragm rapsyn associates with synaptic as well as with extrasynaptic AChRs showing that rapsyn interacts with unclustered AChRs in vivo. Interestingly, synaptic AChRs are associated with more rapsyn suggesting that clustering of AChRs may require increased interaction with rapsyn. In similar experiments in cultured myotubes, rapsyn interacted with intracellular AChRs and with unclustered AChRs at the cell surface, although surface interactions are much more prominent. Remarkably, agrin induces recruitment of additional rapsyn to surface AChRs and clustering of AChRs independently of the secretory pathway. This agrin-induced increase in rapsyn-AChR interaction strongly correlates with clustering, because staurosporine and herbimycin blocked both the increase and clustering. Conversely, laminin and calcium induced both increased rapsynAChR interaction and AChR clustering. Finally, time course experiments revealed that the agrin-induced increase occurs with AChRs that become cytoskeletally linked, and that this precedes receptor clustering. Thus, we propose that neural agrin controls postsynaptic aggregation of the AChR by enhancing rapsyn interaction with surface AChRs and inducing cytoskeletal anchoring and that this is an important precursor step for AChR clustering.

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“…Finally, post-transcriptional mechanisms, including the assembly of the nAChR by the cytoplasmic 43K-rapsyn protein (87,193) into supramolecular aggregates, revealed a progressive compartmentalization of the dispersed nAChR at the subjunctional level (194,195). These studies unveiled the contribution of endogenous trophic factors and electrical activity in the assembly of the subsynaptic membrane (124) and offered a plausible mechanism of long-term synaptic plasticity at the gene expression level.…”

Section: Allosteric Models Of Short-and Long-term Synaptic Plasticitymentioning

confidence: 84%

The Concept of Allosteric Interaction and Its Consequences for the Chemistry of the Brain

Changeux

2013

Journal of Biological Chemistry

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Throughout this Reflections article, I have tried to follow up on the genesis in the 1960s and subsequent evolution of the concept of allosteric interaction and to examine its consequences within the past decades, essentially in the field of the neuroscience. The main conclusion is that allosteric mechanisms built on similar structural principles operate in bacterial regulatory enzymes, gene repressors (and the related nuclear receptors), rhodopsin, G-protein-coupled receptors, neurotransmitter receptors, ion channels, and so on from prokaryotes up to the human brain yet with important features of their own. Thus, future research on these basic cybernetic sensors is expected to develop in two major directions: at the elementary level, toward the atomic structure and molecular dynamics of the conformational changes involved in signal recognition and transduction, but also at a higher level of organization, the contribution of allosteric mechanisms to the modulation of brain functions. Theory in BiologyI n the physical sciences, there is a long tradition of theory and model building; the advancement of the discipline has relied and still relies on an active interplay between theory and experimental studies and between the development of novel technologies and conceptual invention. In the biological sciences, a similar tradition exists, but it is not as systematic. The frequent enthusiasm for new techniques without explicit theoretical perspectives often hides an impoverished theoretical landscape where original hypotheses or ideas are rare. In my view, the theoretical objectives should precede, or be concomitant with, the technological and experimental means. According to Claude Bernard, "the experimenter who does not know what he is looking for will not understand what he finds" (1).1 The reasons for the difficulties encountered with the biological sciences possibly lie in the fact that the objects of biology are highly differentiated with multiple, intricate levels of organization. The identification of common conceptual rules further hinges on the considerable structural and functional diversity of the biological objects. Thus, there is the constant dilemma, often split between scientists, about the universality or the singularity of the objects they investigate. In this context, I have selected as a tentative common rule the concept of allosteric interaction and its consequences on the molecular chemistry of proteins, going from bacterial regulatory enzymes up to the nervous system and, tentatively, the higher functions of the brain.The circumstances of my personal life have been such that as an adolescent, I was already exposed to theory through the teaching of an exceptional professor of natural sciences, Jean Bathellier, who introduced me to the idea of biological evolution. This experience deeply influ-1 The full quote (see Ref. 255) is, "Empiricism may serve to accumulate facts, but it will never build science. The experimenter who does not know what he is looking for will not understand what he finds."

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The rotational diffusion of the acetylcholine receptor in Torpeda marmorata membrane fragments studied with a spin-labelled alpha-toxin: importance of the 43 000 protein(s).

Cited by 88 publications

References 36 publications

Immunofluorescence localization at the mammalian neuromuscular junction of the Mr 43,000 protein of Torpedo postsynaptic membranes.

Immunofluorescence localization at the mammalian neuromuscular junction of the Mr 43,000 protein of Torpedo postsynaptic membranes.

Agrin Regulates Rapsyn Interaction with Surface Acetylcholine Receptors, and This Underlies Cytoskeletal Anchoring and Clustering

The Concept of Allosteric Interaction and Its Consequences for the Chemistry of the Brain

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