Page last updated: 2024-10-24

calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules

Definition

Target type: biologicalprocess

The attachment of one cell to another cell via adhesion molecules that require the presence of calcium for the interaction. [GOC:hb]

Calcium-dependent cell-cell adhesion, mediated by plasma membrane cell adhesion molecules, is a crucial process in multicellular organisms, contributing to tissue formation, morphogenesis, and maintaining tissue integrity. This process involves a complex interplay of transmembrane proteins, intracellular signaling pathways, and the dynamic regulation of calcium ions.

**Adhesion Molecules:**

* **Cadherins:** These transmembrane proteins play a pivotal role in calcium-dependent adhesion. They are characterized by their extracellular domains containing repeated motifs called cadherin repeats, which bind to similar repeats on opposing cadherins, forming strong adhesive junctions. The cytoplasmic tail of cadherins interacts with intracellular proteins like catenins, linking the adhesion complex to the actin cytoskeleton.
* **Selectins:** These transmembrane proteins mediate transient cell-cell interactions, particularly important in leukocyte adhesion and migration. They possess an extracellular lectin domain that binds to specific carbohydrate structures on other cells.

**Calcium's Role:**

* **Binding and Conformation:** Calcium ions bind to specific sites within the extracellular domain of cadherins. This binding is essential for the proper conformation and stability of the cadherin molecules, enabling their association with opposing cadherins to form adhesive junctions.
* **Regulation:** Calcium levels can influence the strength and dynamics of cell-cell adhesion. Increases in intracellular calcium can weaken adhesion, allowing cells to detach and migrate, while decreases in calcium can strengthen adhesion, promoting cell-cell interactions.

**Process Overview:**

1. **Initial Contact:** Cells initiate contact through weak, transient interactions mediated by various cell surface molecules.
2. **Cadherin Clustering:** Cadherins, localized at cell-cell contact sites, begin to cluster upon initial contact.
3. **Calcium Binding:** Calcium ions bind to cadherins, promoting their conformational change and strengthening the adhesive interactions.
4. **Adhesive Junction Formation:** The clustered cadherins, stabilized by calcium binding, form mature adhesive junctions, known as adherens junctions.
5. **Cytoskeletal Linkage:** The intracellular domains of cadherins interact with catenins, which link to the actin cytoskeleton, providing structural support and stability to the adhesive junctions.
6. **Signal Transduction:** Cadherins, upon adhesion, can initiate intracellular signaling pathways, influencing cell behavior, differentiation, and proliferation.

**Biological Significance:**

* **Tissue Formation and Morphogenesis:** Calcium-dependent adhesion is fundamental for the assembly and organization of cells into tissues.
* **Tissue Integrity:** This adhesion maintains tissue integrity, preventing cell separation and ensuring proper organ function.
* **Cell Migration and Differentiation:** The dynamic regulation of adhesion by calcium allows for controlled cell migration, essential for developmental processes, wound healing, and immune responses.
* **Pathological Roles:** Dysregulation of calcium-dependent adhesion can contribute to various diseases, including cancer, inflammation, and developmental disorders.

**In summary, calcium-dependent cell-cell adhesion mediated by plasma membrane cell adhesion molecules is a tightly regulated process that involves the interplay of specific transmembrane proteins, calcium ions, and intracellular signaling pathways. This process is crucial for various biological functions, including tissue formation, morphogenesis, and maintaining tissue integrity, highlighting its central role in multicellular life.**"

Proteins (3)

ProteinDefinitionTaxonomy
Cadherin-1A cadherin-1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P12830]Homo sapiens (human)
P-selectinA P-selectin that is encoded in the genome of human. [PRO:WCB, UniProtKB:P16109]Homo sapiens (human)
L-selectinAn L-selectin that is encoded in the genome of human. [PRO:JAN, UniProtKB:P14151]Homo sapiens (human)

Compounds (11)

CompoundDefinitionClassesRoles
gallic acidgallate : A trihydroxybenzoate that is the conjugate base of gallic acid.trihydroxybenzoic acidantineoplastic agent;
antioxidant;
apoptosis inducer;
astringent;
cyclooxygenase 2 inhibitor;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
geroprotector;
human xenobiotic metabolite;
plant metabolite
oxycinchophenquinolines
2,3,4-Trihydroxybenzoic acidhydroxybenzoic acid
salvinsalvin: a biocyclic diterpenoid; from sage and rosemary (Lamiaceae)abietane diterpenoid;
carbotricyclic compound;
catechols;
monocarboxylic acid
angiogenesis modulating agent;
anti-inflammatory agent;
antineoplastic agent;
antioxidant;
apoptosis inducer;
food preservative;
HIV protease inhibitor;
plant metabolite
toxoflavintoxoflavin : A pyrimidotriazine that is 1,6-dimethyl-1,5,6,7-tetrahydropyrimido[5,4-e][1,2,4]triazine with oxo groups at positions 5 and 7.

toxoflavin: azapteridine antibiotic; structure
carbonyl compound;
pyrimidotriazine
antibacterial agent;
antineoplastic agent;
apoptosis inducer;
bacterial metabolite;
toxin;
virulence factor;
Wnt signalling inhibitor
sulfoquinovosyl dipalmitoyl glyceridesulfoquinovosyl dipalmitoyl glyceride: P-selectin receptor inhibitor; isolated from the alga Dictyochloris fragrans; structure in first source
cercosporincercosporin : An organic heterohexacyclic compound that is perylo[1,12-def][1,3]dioxepine-6,11-dione substituted by hydroxy groups at positions 5 and 12, by methoxy groups at positions 7 and 10, and by 2-hydroxypropyl groups at positions 8 and 9 (the R,R-stereoisomer). It is a phytotoxin which was first isolated from the pathogenic soybean fungus, Cercospora kikuchii and later found in multiple members of the genus Cercospora.

cercosporin: phyytotoxin from Cercospora beticola Sacc; posses photodynamic action on mice, bacteria & plants
bimosiamosebimosiamose: a selectin inhibitor
ucn 1028 ccalphostin C: structure given in first source; isolated from Cladosporium cladosporioides
psi 6972-(4-chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo(H)quinoline-4-carboxylic acid: inhibitor of P selectin that decreases vein wall injury in a rat stenosis model of venous thrombosis
galactocerebrosidegalactocerebroside: a NITROGEN containing sphingolipid