dc.contributor.author
Bathe-Peters, Marc
dc.contributor.author
Gmach, Philipp
dc.contributor.author
Boltz, Horst-Holger
dc.contributor.author
Einsiedel, Jürgen
dc.contributor.author
Gotthardt, Michael
dc.contributor.author
Hübner, Harald
dc.contributor.author
Gmeiner, Peter
dc.contributor.author
Lohse, Martin J.
dc.contributor.author
Annibale, Paolo
dc.date.accessioned
2021-11-11T08:59:50Z
dc.date.available
2021-11-11T08:59:50Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/32665
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-32389
dc.description.abstract
A key question in receptor signaling is how specificity is realized, particularly when different receptors trigger the same biochemical pathway(s). A notable case is the two β‐adrenergic receptor (β‐AR) subtypes, β1 and β2, in cardiomyocytes. They are both coupled to stimulatory Gs proteins, mediate an increase in cyclic adenosine monophosphate (cAMP), and stimulate cardiac contractility; however, other effects, such as changes in gene transcription leading to cardiac hypertrophy, are prominent only for β1‐AR but not for β2-AR. Here, we employ highly sensitive fluorescence spectroscopy approaches, in combination with a fluorescent β‐AR antagonist, to determine the presence and dynamics of the endogenous receptors on the outer plasma membrane as well as on the T-tubular network of intact adult cardiomyocytes. These techniques allow us to visualize that the β2‐AR is confined to and diffuses within the T-tubular network, as opposed to the β1‐AR, which is found to diffuse both on the outer plasma membrane as well as on the T-tubules. Upon overexpression of the β2‐AR, this compartmentalization is lost, and the receptors are also seen on the cell surface. Such receptor segregation depends on the development of the T-tubular network in adult cardiomyocytes since both the cardiomyoblast cell line H9c2 and the cardiomyocyte-differentiated human-induced pluripotent stem cells express the β2‐AR on the outer plasma membrane. These data support the notion that specific cell surface targeting of receptor subtypes can be the basis for distinct signaling and functional effects.
en
dc.format.extent
10 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
β-adrenergic receptors
en
dc.subject
cardiomyocyte
en
dc.subject
fluorescence microscopy
en
dc.subject
fluorescence
en
dc.subject
correlation spectroscopy
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::540 Chemie::540 Chemie und zugeordnete Wissenschaften
dc.title
Visualization of β-adrenergic receptor dynamics and differential localization in cardiomyocytes
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
e2101119118
dcterms.bibliographicCitation.doi
10.1073/pnas.2101119118
dcterms.bibliographicCitation.journaltitle
Proceedings of the National Academy of Sciences (PNAS)
dcterms.bibliographicCitation.number
23
dcterms.bibliographicCitation.volume
118
dcterms.bibliographicCitation.url
https://doi.org/10.1073/pnas.2101119118
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Chemie und Biochemie
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1091-6490
refubium.resourceType.provider
WoS-Alert