Contraction is the basis of skeletal muscle function. This is made possible by the excitation contraction coupling (ECC) mechanism occurring at triads, membrane structures formed by the apposition of two terminal cisternae of the sarcoplasmic reticulum and one T-tubule, an invagination of the plasma membrane. At triads, many proteins contribute to ECC and in maintenance of this pivotal structure. Among them, Junctophillins (JPHs) play an essential role in triad formation and ECC regulation by acting as molecular bridges between T-tubules and the terminal cisternae of the j-SR and by interacting with many proteins of the Ca2+ release machinery. By using the Proximity-dependent labelling with BioID2 we identified Climp63 as a novel interactor of JPHs. Climp63 is a non-muscle specific protein, involved in endoplasmic reticulum shaping and interaction with the microtubular network. Interaction between JPHs and Climp63 has been confirmed by co-immunoprecipitation experiments that showed that Climp63 is part of a multiprotein complex including JPHs, triadin and junctin. Preliminary experiment indicate that Climp63 specifically interacts with JPHs, but not with members of another protein family mediating the formation of membrane contact sites; this interaction is suggested to be mediated by the transmembrane regions of JPHs and Climp63. Analysis of the expression pattern of Climp63 during skeletal muscle differentiation showed that Climp63 is predominately expressed in the embryonic and first weeks of life, suggesting that it may play a role in the first steps of sarcoplasmic reticulum remodelling to form mature triad

Amadsun, D. (2023). Junctophilins and Climp63: a novel interaction in skeletal muscle [10.25434/david-osamwonuyi-amadsun_phd2023].

Junctophilins and Climp63: a novel interaction in skeletal muscle

David Osamwonuyi Amadsun
2023-01-01

Abstract

Contraction is the basis of skeletal muscle function. This is made possible by the excitation contraction coupling (ECC) mechanism occurring at triads, membrane structures formed by the apposition of two terminal cisternae of the sarcoplasmic reticulum and one T-tubule, an invagination of the plasma membrane. At triads, many proteins contribute to ECC and in maintenance of this pivotal structure. Among them, Junctophillins (JPHs) play an essential role in triad formation and ECC regulation by acting as molecular bridges between T-tubules and the terminal cisternae of the j-SR and by interacting with many proteins of the Ca2+ release machinery. By using the Proximity-dependent labelling with BioID2 we identified Climp63 as a novel interactor of JPHs. Climp63 is a non-muscle specific protein, involved in endoplasmic reticulum shaping and interaction with the microtubular network. Interaction between JPHs and Climp63 has been confirmed by co-immunoprecipitation experiments that showed that Climp63 is part of a multiprotein complex including JPHs, triadin and junctin. Preliminary experiment indicate that Climp63 specifically interacts with JPHs, but not with members of another protein family mediating the formation of membrane contact sites; this interaction is suggested to be mediated by the transmembrane regions of JPHs and Climp63. Analysis of the expression pattern of Climp63 during skeletal muscle differentiation showed that Climp63 is predominately expressed in the embryonic and first weeks of life, suggesting that it may play a role in the first steps of sarcoplasmic reticulum remodelling to form mature triad
2023
35
Amadsun, D. (2023). Junctophilins and Climp63: a novel interaction in skeletal muscle [10.25434/david-osamwonuyi-amadsun_phd2023].
Amadsun, DAVID-OSAMWONUYI
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1231594