RESUMEN
Desmosomes play a critical role in maintaining tissue barrier integrity, particularly in mechanically stressed tissues. The assembly of desmosomes is regulated by the cytoskeleton and its regulators, while desmosomes also function as a central hub for regulating F-actin. However, the specific mechanisms underlying the crosstalk between desmosomes and F-actin remain unclear. Here, we identified that ARHGAP32, a Rho GTPase-activating protein, is located in desmosomes through its interaction with DSP via its GAB2-interacting domain (GAB2-ID). We confirmed that ARHGAP32 is required for desmosomal organization, maturation, and length regulation. Notably, loss of ARHGAP32 increased formation of F-actin stress fibers and phosphorylation of Myosin at T18/S19. Inhibition of ROCK1 activity in ARHGAP32 KO cells effectively restored desmosomal organization and the integrity of epithelial cell sheets. Moreover, loss of DSP impaired desmosomal ARHGAP32 while decreased actomyosin contractility. Deletion of the GAB2-ID of ARHGAP32 enhanced its association with RHOA in the cytosol and failed to rescue the desmosomal organization. Collectively, our study unveils ARHGAP32 associates with and regulates desmosomes by interacting with DSP. This interaction potentially facilitates the crosstalk between desmosomes and F-actin.
RESUMEN
Cell-cell mechanotransduction regulates tissue development and homeostasis. α-catenin, the core component of adherens junctions, functions as a tension sensor and transducer by recruiting vinculin and transducing signals that influence cell behaviors. α-catenin/vinculin complex-mediated mechanotransduction regulates multiple pathways, such as Hippo pathway. However, their associations with the α-catenin-based tension sensors at cell junctions are still not fully addressed. Here, we uncovered the TRIP6/LATS1 complex co-localizes with α-catenin/vinculin at both bicellular junctions (BCJs) and tricellular junctions (TCJs). The localization of TRIP6/LATS1 complex to both TCJs and BCJs requires ROCK1 and α-catenin. Treatment by cytochalasin B, Y-27632 and blebbistatin all impaired the BCJ and TCJ junctional localization of TRIP6/LATS1, indicating that the junctional localization of TRIP6/LATS1 is mechanosensitive. The α-catenin/vinculin/TRIP6/LATS1 complex strongly localized to TCJs and exhibited a discontinuous button-like pattern on BCJs. Additionally, we developed and validated an α-catenin/vinculin BiFC-based mechanosensor that co-localizes with TRIP6/LATS1 at BCJs and TCJs. The mechanosensor exhibited a discontinuous distribution and motile signals at BCJs. Overall, our study revealed that TRIP6 and LATS1 are novel compositions of the tension sensor, together with the core complex of α-catenin/vinculin, at both the BCJs and TCJs.
Asunto(s)
Proteínas Serina-Treonina Quinasas , Vinculina , alfa Catenina , alfa Catenina/metabolismo , Humanos , Proteínas Serina-Treonina Quinasas/metabolismo , Vinculina/metabolismo , Mecanotransducción Celular , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Uniones Intercelulares/metabolismo , Células HEK293 , Quinasas Asociadas a rho/metabolismo , Factores de Transcripción/metabolismoRESUMEN
It is known that as the FeAs4 tetrahedron in the Fe-based superconductor is close to the regular tetrahedron, critical temperature (Tc) can be greatly increased. Recently, a Co-based superconductor of LaCoSi (4 K) with "111" structure was found. In this work, we improve the Tc of LaCoSi through structural regulation. Tc can be increased by the chemical substitution of Co by Fe, while the superconductivity is suppressed by the Ni substitution. The combined analysis of neutron and synchrotron X-ray powder diffractions reveals that the change of the Si-Co-Si bond angles of the CoSi4 tetrahedron is possibly responsible for the determination of superconducting properties. The Fe chemical substitution is favorable for the formation of the regular tetrahedron of CoSi4. The present new Co-based superconductor of LaCoSi provides a possible method to enhance the superconductivity performance of the Co-based superconductors via controlling Co-based tetrahedra similar to those well established in the Fe-based superconductors.
RESUMEN
It is known that few Co-based superconducting compounds have been found compared with their Fe- or Ni-based counterparts. In this study, we have found superconductivity of 4 K in the LaCoSi compound for the first time. The combined analysis of neutron and synchrotron X-ray powder diffractions reveals that LaCoSi exhibits an isostructure with the known Fe-based LiFeAs superconductor, which is the first "111" Co-based superconductor. First-principles calculation shows that LaCoSi presents a quasi-two-dimensional band structure that is also similar to that of LiFeAs. The small structural distortion may be more conducive to the emergence of superconductivity in the LaCoSi compound, which provides a direction for finding new Co-based superconducting compounds.