scholarly journals Cis-clustering of cadherin-23 controls the kinetics of cell-cell adhesion

2021 ◽  
Author(s):  
Sabyasachi Rakshit ◽  
Cheerneni Srini ◽  
Gayathri Singaraju ◽  
Nisha Arora ◽  
Sayan Das ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Single Molecule ◽  
Liquid Droplets ◽  
Extracellular Region ◽  
Cadherin 23 ◽  
Multicellular Organisms ◽  
Cis And Trans ◽  
Kinetics Of ◽  
Cis Interaction ◽  
Cell Cell

Abstract Cis and trans-interactions in cadherins are the foundations of cellular adhesions in multicellular organisms. While the trans-interactions mediate the intercellular attachment, the cis-interaction is presumed as reinforcement to trans. Thus, trans precedes cis has been the well-accepted model in cadherin adhesion. The stronger affinity of trans-binding over cis has been the decisive influence in the trans first model. Here we show that cadherin-23, a non-classical cadherin with an extended extracellular region, can undergo cis-clustering in solution independent of trans and phase separate as liquid droplets. Using single-molecule measurements, we decipher that weaker cis-interactions favor the cis-clustering. In-cellulo, the cis-clustering is manifested as puncta, a common feature in non-classical cadherin junctions, and accelerates the cell adhesion. The cis-clustering thus kinetically controls cell-adhesion before trans-binding. Notably, M2-macrophages predominantly express cadherin-23 and rapidly attach to circulatory tumor cells during metastatic migration. However, the relation of cis-clustering with rapid cell-cell adhesion in physiology is not yet established

scholarly journals Cis-clustering of cadherin-23 controls the kinetics of cell-cell adhesion

2022 ◽  
Author(s):  
Cheerneni Sai Srinivas ◽  
Gayathri Sindhuri Singaraju ◽  
Sayan Das ◽  
Amin Sagar ◽  
Anuj Kumar ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Intercellular Junctions ◽  
Liquid Droplets ◽  
Extracellular Region ◽  
Cadherin 23 ◽  
Mediate Cell ◽  
Cis And Trans ◽  
Kinetics Of ◽  
Cis Interaction ◽  
Cell Cell

Cis and trans-interactions in cadherins are the foundations of multicellularity. While the trans-interaction mediate cell-cell adhesion, the cis-interaction is postulated as strengthening to trans by clustering. The well-accepted model in cadherin-adhesion is that the trans precedes cis via a diffusion-trap kinetic model. Here we report that cadherin-23, a non-classical cadherin with an extended extracellular region, undergoes clustering in solution via lateral interactions independent of trans and phase separate as liquid droplets. In cellulo using fluorescence-recovery after the photobleaching, we noticed a significantly slow-diffusion of cadherin-23 at the intercellular junctions, indicating the diffusion of a cluster. The cis-clustering accelerates the cell-cell adhesion and, thus, kinetically controls cell-adhesion via cis precedes trans model. Though the connection of cis-clustering with the rapid adhesion is yet to explore, M2-macrophages that predominantly express cadherin-23 undergo fast attachments to circulatory tumor cells during metastasis.

scholarly journals Cis-Clustering of Cadherin-23 Controls the Kinetics of Cell-Cell Adhesion

2021 ◽  
Author(s):  
Cheerneni Sai Srinivas ◽  
Gayathri Sindhuri Singaraju ◽  
Nisha Arora ◽  
Sayan Das ◽  
Amin Sagar ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cadherin 23 ◽  
Kinetics Of ◽  
Cell Cell

scholarly journals Molecular mechanism of cell-cell adhesion mediated by cadherin-23

2017 ◽  
Author(s):  
G. S. Singaraju ◽  
A. Kumar ◽  
J. S. Samuel ◽  
A. Sagar ◽  
J. P. Hazra ◽  
...  
Keyword(s):  
Single Molecule ◽  
Single Point ◽  
Cell Junctions ◽  
Single Point Mutation ◽  
Molecular Architecture ◽  
Binding Interface ◽  
Extracellular Region ◽  
Classical Cadherins ◽  
Cadherin 23 ◽  
Cell Cell

AbstractAdherin-junctions are traditionally described by the homophilic-interactions of classical cadherin-proteins at the extracellular region. However, the role of long-chain non-classical cadherins like cadherin-23(Cdh23) is not explored as yet even though it is implicated in tissue-morphogenesis, cancer, and force-sensing in neuronal tissues. Here, we identified a novel antiparallel-binding interface of Cdh23 homodimer in solution by combining biophysical and computational methods, in-vitro cell-binding, and mutational modifications. The dimer consists of two electrostatic-based interfaces extended up to two terminal domains, atypical to classical-cadherins known so far, and forms the strongest interactions in cadherin-family as measured using single-molecule force-spectroscopy. We further identified single point-mutation, E78K, that completely disrupts this binding. Interestingly, the mutation, S77L, found in skin cancers falls within the binding interface of the antiparallel-dimer. Overall, we provide the molecular architecture of Cdh23 at the cell-cell junctions which are likely to have far-reaching applications in the fields of mechanobiology and cancer.

scholarly journals Cell–cell adhesion in plant grafting is facilitated by β-1,4-glucanases

2020 ◽  
Author(s):  
Michitaka Notaguchi ◽  
Ken-ichi Kurotani ◽  
Yoshikatsu Sato ◽  
Ryo Tabata ◽  
Yaichi Kawakatsu ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Fruit Trees ◽  
Living Tissue ◽  
Closely Related Species ◽  
Tomato Fruits ◽  
Diverse Range ◽  
Extracellular Region ◽  
Plant Families ◽  
Graft Interface ◽  
Cell Cell

Plant grafting is conducted for vegetative propagation in plants, whereby a piece of living tissue is attached to another tissue through establishment of cell–cell adhesion. Plant grafting has a long history in agriculture and has been applied to improve crop traits for thousands of years1. Plant grafting has mostly relied on the natural ability of a plant for wound healing. However, the compatibility of cell–cell adhesion typically limits graft combinations to closely related species2–4, and the mechanism by which cell–cell adhesion of injured tissues is established is largely unknown. Here, we show that a subclade of β-1,4-glucanases secreted into the extracellular region facilitates cell–cell adhesion near the graft interface. Nicotiana shows a propensity for cell–cell adhesion with a diverse range of angiosperms, including vegetables, fruit trees, and monocots, in which cell wall reconstruction was promoted in a similar manner to conventional intrafamily grafting5–7. Using transcriptomic approaches, we identified a specific clade of β-1,4-glucanases that is upregulated during grafting in successful graft combinations but not in incompatible grafts and precedes graft adhesion in inter- and intrafamily grafts. Grafting was facilitated with an overexpressor of the β-1,4-glucanase and, using Nicotiana stem as an interscion, we produced tomato fruits on rootstocks from other plant families. Our results demonstrate that the mechanism of cell–cell adhesion is partly conserved in plants and is a potential target to enhance plant grafting techniques.

Emergence of Multicellular Organisms with Dynamic Differentiation and Spatial Pattern

1998 ◽  
Vol 4 (1) ◽  
pp. 79-93 ◽  
Author(s):  
Chikara Furusawa ◽  
Kunihiko Kaneko
Keyword(s):  
Cell Adhesion ◽  
Spatial Pattern ◽  
Spatial Information ◽  
Adhesion Force ◽  
Cell Interaction ◽  
Dynamical Instability ◽  
Differentiated Cells ◽  
State Dependent ◽  
Multicellular Organisms ◽  
Cell Cell

The origin of multicellular organisms and the mechanism of development in cell societies are studied by choosing a model with intracellular biochemical dynamics allowing for oscillations, cell–cell interaction through diffusive chemicals on a two-dimensional grid, and state-dependent cell adhesion. Cells differentiate due to a dynamical instability, as described by our “isologous diversification” theory. A fixed spatial pattern of differentiated cells emerges, where spatial information is sustained by cell–cell interactions. This pattern is robust against perturbations. With an adequate cell adhesion force, active cells are released that form the seed of a new generation of multicellular organisms, accompanied by death of the original multicellular unit as a halting state. It is shown that the emergence of multicellular organisms with differentiation, regulation, and life cycle is not an accidental event, but a natural consequence in a system of replicating cells with growth.

scholarly journals Molecular basis of sidekick-mediated cell-cell adhesion and specificity

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Kerry M Goodman ◽  
Masahito Yamagata ◽  
Xiangshu Jin ◽  
Seetha Mannepalli ◽  
Phinikoula S Katsamba ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Aggregation ◽  
Immunoglobulin Superfamily ◽  
Retinal Neurons ◽  
Isolated Cells ◽  
Recognition Specificity ◽  
Mediate Cell ◽  
Cis And Trans ◽  
Cell Adhesion Proteins ◽  
Cell Cell

Sidekick (Sdk) 1 and 2 are related immunoglobulin superfamily cell adhesion proteins required for appropriate synaptic connections between specific subtypes of retinal neurons. Sdks mediate cell-cell adhesion with homophilic specificity that underlies their neuronal targeting function. Here we report crystal structures of Sdk1 and Sdk2 ectodomain regions, revealing similar homodimers mediated by the four N-terminal immunoglobulin domains (Ig1–4), arranged in a horseshoe conformation. These Ig1–4 horseshoes interact in a novel back-to-back orientation in both homodimers through Ig1:Ig2, Ig1:Ig1 and Ig3:Ig4 interactions. Structure-guided mutagenesis results show that this canonical dimer is required for both Sdk-mediated cell aggregation (via trans interactions) and Sdk clustering in isolated cells (via cis interactions). Sdk1/Sdk2 recognition specificity is encoded across Ig1–4, with Ig1–2 conferring the majority of binding affinity and differential specificity. We suggest that competition between cis and trans interactions provides a novel mechanism to sharpen the specificity of cell-cell interactions.

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