scholarly journals Disease mutations in desmoplakin inhibit Cx43 membrane targeting mediated by desmoplakin–EB1 interactions

2014 ◽  
Vol 206 (6) ◽  
pp. 779-797 ◽  
Author(s):  
Dipal M. Patel ◽  
Adi D. Dubash ◽  
Geri Kreitzer ◽  
Kathleen J. Green
Keyword(s):  
Gap Junction ◽  
Cell Contact ◽  
Membrane Targeting ◽  
Microtubule Organization ◽  
Disease Mutations ◽  
Skin Fragility ◽  
Woolly Hair ◽  
And Function ◽  
Desmosomal Protein ◽  
Cell Cell

Mechanisms by which microtubule plus ends interact with regions of cell–cell contact during tissue development and morphogenesis are not fully understood. We characterize a previously unreported interaction between the microtubule binding protein end-binding 1 (EB1) and the desmosomal protein desmoplakin (DP), and demonstrate that DP–EB1 interactions enable DP to modify microtubule organization and dynamics near sites of cell–cell contact. EB1 interacts with a region of the DP N terminus containing a hotspot for pathogenic mutations associated with arrhythmogenic cardiomyopathy (AC). We show that a subset of AC mutations, in addition to a mutation associated with skin fragility/woolly hair syndrome, impair gap junction localization and function by misregulating DP–EB1 interactions and altering microtubule dynamics. This work identifies a novel function for a desmosomal protein in regulating microtubules that affect membrane targeting of gap junction components, and elucidates a mechanism by which DP mutations may contribute to the development of cardiac and cutaneous diseases.

scholarly journals Control of exocytotic processes: cytological and physiological studies of trichocyst mutants in Paramecium tetraurelia.

1981 ◽  
Vol 88 (2) ◽  
pp. 301-311 ◽  
Author(s):  
M Lefort-Tran ◽  
K Aufderheide ◽  
M Pouphile ◽  
M Rossignol ◽  
J Beisson
Keyword(s):  
Plasma Membrane ◽  
Freeze Fracture ◽  
Cell Interaction ◽  
Secretory Vesicle ◽  
Secretory Process ◽  
Cell Contact ◽  
Paramecium Tetraurelia ◽  
Cytoplasmic Factor ◽  
And Function ◽  
Cell Cell

The trichocysts of Paramecium tetraurelia constitute a favorable system for studying secretory process because of the numerous available mutations that block, at various stages, the development of these secretory vesicles, their migration towards and interaction with the cell surface, and their exocytosis. Previous studies of several mutants provided information (a) on the assembly and function of the intramembranous particles arrays in the plasma membrane at trichocyst attachment sites, (b) on the autonomous motility of trichocysts, required for attachment to the cortex, and (c) on a diffusible cytoplasmic factor whose interaction with both trichocyst and plasma membrane is required for exocytosis to take place. We describe here the properties of four more mutants deficient in exocytosis ability, nd6, nd7, tam38, and tam6, which were analyzed by freeze-fracture, microinjection of trichocysts, and assay for repair of the mutational defect through cell-cell interaction during conjugation with wild-type cells. As well as providing confirmation of previous conclusions, our observations show that the mutations nd6 and tam6 (which display striking abnormalities in their plasma membrane particle arrays and are reparable through cell-cell contact but not by microinjection of cytoplasm) affect two distinct properties of the plasma membrane, whereas the other two mutations affect different properties of the trichocysts. Altogether, the mutants so far analyzed now provide a rather comprehensive view of the steps and functions involved in secretory processes in Paramecium and demonstrate that two steps of these processes, trichocyst attachment to the plasma membrane and exocytosis, depend upon specific properties of both the secretory vesicle and the plasma membrane.

scholarly journals The envelope cytoplasmic tail regulates HIV-1 assembly and spread

2021 ◽  
Author(s):  
Xenia Snetkov ◽  
Tafhima Haider ◽  
Dejan Mesner ◽  
Nicholas Groves ◽  
Schuyler van Engelenburg ◽  
...  
Keyword(s):  
T Cells ◽  
Structural Integrity ◽  
Alpha Helix ◽  
Cytoplasmic Tail ◽  
Virological Synapse ◽  
Cell Contact ◽  
Viral Fusion ◽  
And Function ◽  
Hiv 1 ◽  
Cell Cell

AbstractThe HIV-1 envelope (Env) is an essential determinant of viral infectivity, tropism and spread between T cells. Lentiviral Env contain an unusually long 150 amino acid cytoplasmic tail (EnvCT) but the function of the EnvCT and conserved domains within it remain largely uncharacterised. Here we identified a highly conserved tryptophan motif at position 757 (W757) in the LLP-2 alpha helix of the EnvCT as a key determinant for HIV-1 replication and spread between T cells. Strikingly we find that mutating W757 had wide-ranging consequences including altering Env mobility in the plasma membrane, preventing Env and Gag recruitment to sites of cell-cell contact for virological synapse (VS) formation and cell-cell spread, and impeding viral fusion. Notably, W757 was also required for efficient virus budding, revealing a previously unappreciated role for the EnvCT in regulating HIV-1 assembly and egress. We conclude that W757 is a key residue that stabilises the structural integrity and function of Env, consistent with the recent model that this region of the EnvCT acts as a critical supporting baseplate for Env.

scholarly journals Redox-Sensitive Structure and Function of the First Extracellular Loop of the Cell–Cell Contact Protein Claudin-1: Lessons from Molecular Structure to Animals

2015 ◽  
Vol 22 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Sebastian Dabrowski ◽  
Christian Staat ◽  
Denise Zwanziger ◽  
Reine-Solange Sauer ◽  
Christian Bellmann ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Structure And Function ◽  
Cell Contact ◽  
Extracellular Loop ◽  
Sensitive Structure ◽  
And Function ◽  
Cell Cell

scholarly journals Matrix Stiffness Modulates Mechanical Interactions and Promotes Contact between Motile Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 428
Author(s):  
Subhaya Bose ◽  
Kinjal Dasbiswas ◽  
Arvind Gopinath
Keyword(s):  
Cell Motility ◽  
Cell Structure ◽  
Biophysical Model ◽  
Cell Contact ◽  
Mechanical Deformations ◽  
Range Cell ◽  
Permanent Cell ◽  
Key Aspects ◽  
And Function ◽  
Cell Cell

The mechanical micro-environment of cells and tissues influences key aspects of cell structure and function, including cell motility. For proper tissue development, cells need to migrate, interact, and form contacts. Cells are known to exert contractile forces on underlying soft substrates and sense deformations in them. Here, we propose and analyze a minimal biophysical model for cell migration and long-range cell–cell interactions through mutual mechanical deformations of the substrate. We compute key metrics of cell motile behavior, such as the number of cell-cell contacts over a given time, the dispersion of cell trajectories, and the probability of permanent cell contact, and analyze how these depend on a cell motility parameter and substrate stiffness. Our results elucidate how cells may sense each other mechanically and generate coordinated movements and provide an extensible framework to further address both mechanical and short-range biophysical interactions.

scholarly journals Transforming growth factor-β1-induced N-cadherin drives cell–cell communication through connexin43 in osteoblast lineage

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Yueyi Yang ◽  
Wenjing Liu ◽  
JieYa Wei ◽  
Yujia Cui ◽  
Demao Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gap Junction ◽  
Cell Line ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Cx43 Expression ◽  
Mc3t3 Cell ◽  
Primary Osteoblasts ◽  
Tgf Β1 ◽  
Cell Cell

AbstractGap junction (GJ) has been indicated to have an intimate correlation with adhesion junction. However, the direct interaction between them partially remains elusive. In the current study, we aimed to elucidate the role of N-cadherin, one of the core components in adhesion junction, in mediating connexin 43, one of the functional constituents in gap junction, via transforming growth factor-β1(TGF-β1) induction in osteoblasts. We first elucidated the expressions of N-cadherin induced by TGF-β1 and also confirmed the upregulation of Cx43, and the enhancement of functional gap junctional intercellular communication (GJIC) triggered by TGF-β1 in both primary osteoblasts and MC3T3 cell line. Colocalization analysis and Co-IP experimentation showed that N-cadherin interacts with Cx43 at the site of cell–cell contact. Knockdown of N-cadherin by siRNA interference decreased the Cx43 expression and abolished the promoting effect of TGF-β1 on Cx43. Functional GJICs in living primary osteoblasts and MC3T3 cell line were also reduced. TGF-β1-induced increase in N-cadherin and Cx43 was via Smad3 activation, whereas knockdown of Smad3 signaling by using siRNA decreased the expressions of both N-cadherin and Cx43. Overall, these data indicate the direct interactions between N-cadherin and Cx43, and reveal the intervention of adhesion junction in functional gap junction in living osteoblasts.

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