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dc.contributor.authorSato, Daisuke
dc.contributor.authorHernández-Hernández, Gonzalo
dc.contributor.authorMatsumoto, Collin
dc.contributor.authorTajada, Sendoa
dc.contributor.authorMoreno, Claudia M.
dc.contributor.authorDixon, Rose E.
dc.contributor.authorO’Dwyer, Samantha
dc.contributor.authorNavedo, Manuel F.
dc.contributor.authorTrimmer, James S.
dc.contributor.authorClancy, Colleen E.
dc.contributor.authorBinder, Marc D.
dc.contributor.authorSantana, L. Fernando
dc.date.accessioned2024-02-06T12:36:06Z
dc.date.available2024-02-06T12:36:06Z
dc.date.issued2019
dc.identifier.citationJ Gen Physiol. 2019 Sep 2;151(9):1116-1134.es
dc.identifier.issn0022-1295es
dc.identifier.urihttps://uvadoc.uva.es/handle/10324/65821
dc.description.abstractIon channels are often found arranged into dense clusters in the plasma membranes of excitable cells, but the mechanisms underlying the formation and maintenance of these functional aggregates are unknown. Here, we tested the hypothesis that channel clustering is the consequence of a stochastic self-assembly process and propose a model by which channel clusters are formed and regulated in size. Our hypothesis is based on statistical analyses of the size distributions of the channel clusters we measured in neurons, ventricular myocytes, arterial smooth muscle, and heterologous cells, which in all cases were described by exponential functions, indicative of a Poisson process (i.e., clusters form in a continuous, independent, and memory-less fashion). We were able to reproduce the observed cluster distributions of five different types of channels in the membrane of excitable and tsA-201 cells in simulations using a computer model in which channels are "delivered" to the membrane at randomly assigned locations. The model's three parameters represent channel cluster nucleation, growth, and removal probabilities, the values of which were estimated based on our experimental measurements. We also determined the time course of cluster formation and membrane dwell time for CaV1.2 and TRPV4 channels expressed in tsA-201 cells to constrain our model. In addition, we elaborated a more complex version of our model that incorporated a self-regulating feedback mechanism to shape channel cluster formation. The strong inference we make from our results is that CaV1.2, CaV1.3, BK, and TRPV4 proteins are all randomly inserted into the plasma membranes of excitable cells and that they form homogeneous clusters that increase in size until they reach a steady state. Further, it appears likely that cluster size for a diverse set of membrane-bound proteins and a wide range of cell types is regulated by a common feedback mechanism.es
dc.format.mimetypeapplication/pdfes
dc.language.isospaes
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.titleA stochastic model of ion channel cluster formation in the plasma membranees
dc.typeinfo:eu-repo/semantics/articlees
dc.identifier.doi10.1085/JGP.201912327es
dc.identifier.publicationfirstpage1116es
dc.identifier.publicationissue9es
dc.identifier.publicationlastpage1134es
dc.identifier.publicationtitleJournal of General Physiologyes
dc.identifier.publicationvolume151es
dc.peerreviewedSIes
dc.identifier.essn1540-7748es
dc.type.hasVersioninfo:eu-repo/semantics/draftes


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