Page last updated: 2024-10-24

calcium-independent cell-matrix adhesion

Definition

Target type: biologicalprocess

The binding of a cell to the extracellular matrix via adhesion molecules that do not require the presence of calcium for the interaction. [GOC:hb]

Calcium-independent cell-matrix adhesion is a complex biological process that allows cells to adhere to the extracellular matrix (ECM) without relying on calcium ions. This process is crucial for maintaining tissue integrity, regulating cell behavior, and facilitating various cellular functions. Here's a detailed explanation:

**1. Key Molecules and Mechanisms:**

* **Integrins:** Integrins are transmembrane proteins that play a central role in cell-matrix adhesion. They consist of two subunits, α and β, which combine to form different integrin heterodimers.
* **Non-classical Integrins:** Unlike classical integrins that require calcium for adhesion, non-classical integrins like αvβ3 and αvβ5 are calcium-independent.
* **ECM Ligands:** These are molecules in the extracellular matrix that bind to integrins. Examples include:
* **Fibronectin:** A large glycoprotein that interacts with both classical and non-classical integrins.
* **Vitronectin:** A protein that binds to αvβ3 and αvβ5 integrins.
* **Laminin:** A multi-domain protein found in the basement membrane, often interacting with αvβ6 integrin.

**2. Adhesion Process:**

* **Integrin Binding:** Non-classical integrins bind to their specific ECM ligands, initiating adhesion.
* **Clustering and Aggregation:** Integrins, upon ligand binding, cluster together, forming focal adhesions or other specialized adhesive structures.
* **Signal Transduction:** Integrin binding triggers intracellular signaling cascades that regulate cytoskeletal rearrangements, gene expression, and cell behavior.
* **Focal Adhesion Kinase (FAK):** A key signaling molecule involved in integrin-mediated signaling pathways.
* **Small GTPases:** Proteins like Rac and Rho control cytoskeletal dynamics and cell migration.

**3. Cellular Functions:**

* **Cell Migration:** Calcium-independent cell-matrix adhesion is vital for cell migration, guiding cells along specific pathways.
* **Tissue Development and Repair:** This process is essential for the formation and repair of tissues, ensuring proper organization and stability.
* **Wound Healing:** Cell-matrix adhesion is critical for proper wound closure, involving cell migration and matrix deposition.
* **Angiogenesis:** The formation of new blood vessels is often regulated by calcium-independent cell-matrix interactions.

**4. Regulation and Modulation:**

* **Growth Factors:** Factors like TGF-β and VEGF can influence integrin expression and activity, modulating cell-matrix interactions.
* **Proteases:** Enzymes like matrix metalloproteinases (MMPs) can degrade ECM components, affecting adhesion and cell behavior.
* **Post-translational Modifications:** Integrin activity can be modulated by phosphorylation, glycosylation, and other post-translational modifications.

**5. Implications for Disease:**

* **Cancer Metastasis:** Malignant cells often exploit calcium-independent cell-matrix interactions to invade surrounding tissues and metastasize.
* **Wound Healing Disorders:** Defective cell-matrix adhesion can lead to impaired wound healing and chronic skin ulcers.
* **Vascular Diseases:** Dysregulation of calcium-independent cell-matrix adhesion contributes to cardiovascular problems like atherosclerosis.

In conclusion, calcium-independent cell-matrix adhesion is a fundamental process essential for many aspects of cell biology. Understanding this complex mechanism is crucial for unraveling normal tissue development, wound healing, and disease pathogenesis.'
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Proteins (2)

ProteinDefinitionTaxonomy
Integrin beta-1An integrin beta-1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P05556]Homo sapiens (human)
FibronectinA fibronectin that is encoded in the genome of human. [PRO:DNx, UniProtKB:P02751]Homo sapiens (human)

Compounds (18)

CompoundDefinitionClassesRoles
haloperidolhaloperidol : A compound composed of a central piperidine structure with hydroxy and p-chlorophenyl substituents at position 4 and an N-linked p-fluorobutyrophenone moiety.

Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)
aromatic ketone;
hydroxypiperidine;
monochlorobenzenes;
organofluorine compound;
tertiary alcohol
antidyskinesia agent;
antiemetic;
dopaminergic antagonist;
first generation antipsychotic;
serotonergic antagonist
1,3-ditolylguanidine1,3-ditolylguanidine: structure given in first source; a selective ligand for the sigma binding sites in the braintoluenes
tirofibantirofiban : A member of the class of piperidines that is L-tyrosine in which a hydrogen attached to the amino group is replaced by a butylsulfonyl group and in which the hydrogen attached to the phenolic hydroxy group is replaced by a 4-(piperidin-4-yl)butyl group.

Tirofiban: Tyrosine analog and PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX antagonist that inhibits PLATELET AGGREGATION and is used in the treatment of ACUTE CORONARY SYNDROME.
L-tyrosine derivative;
piperidines;
sulfonamide
anticoagulant;
fibrin modulating drug;
platelet glycoprotein-IIb/IIIa receptor antagonist
arginyl-glycyl-aspartic acidarginyl-glycyl-aspartic acid: amino acid sequence of basic unit of widespread cellular recognition systemoligopeptide
arginyl-glycyl-aspartyl-serinearginyl-glycyl-aspartyl-serine: corresponds to cell attachment site of fibronectin; located near carboxyl-terminal region of alpha-chain of fibrinogen; inhibits platelet aggregation & fibrinogen binding to activated platelets
glycyl-arginyl-glycyl-aspartyl-serineglycyl-arginyl-glycyl-aspartyl-serine: synthetic peptide from fibronectins; inhibits experimental metastasis of murine melanoma cells
d-arg-gly-asp-trparginyl-glycyl-aspartyl-tryptophan: a synthetic RGD-containing peptide
l 738167L 738167: structure in first source
cilengitideCilengitide: an alphaVbeta3 integrin antagonist that paralyzes cancer cellsoligopeptide
l 734217L 734217: fibrinogen receptor antagonist; structure given in first source
cyclopaminepiperidinesglioma-associated oncogene inhibitor
s 1033(trifluoromethyl)benzenes;
imidazoles;
pyridines;
pyrimidines;
secondary amino compound;
secondary carboxamide
anticoronaviral agent;
antineoplastic agent;
tyrosine kinase inhibitor
arginyl-glycyl-aspartyl-phenylalanine
cyclic(arg-gly-asp-d-phe-val)
mk-0429
mocetinostatmocetinostat : A benzamide obtained by formal condensation of the carboxy group of 4-({[4-(pyridin-3-yl)pyrimidin-2-yl]amino}methyl)benzoic acid with one of the amino groups of benzene-1,2-diamine. It is an orally active and isotype-selective HDAC inhibitor which exhibits antitumour activity (IC50 = 0.15, 0.29, 1.66 and 0.59 muM for HDAC1, HDAC2, HDAC3 and HDAC11).

mocetinostat: undergoing phase II clinical trials for treatment of cancer
aminopyrimidine;
benzamides;
pyridines;
secondary amino compound;
secondary carboxamide;
substituted aniline
antineoplastic agent;
apoptosis inducer;
autophagy inducer;
cardioprotective agent;
EC 3.5.1.98 (histone deacetylase) inhibitor;
hepatotoxic agent
tr 14035N-(2,6-dichlorobenzoyl)-4-(2',6'-bismethoxyphenyl)phenylalanine: TR-14035 is the (L)-isomer; an antagonist of both alpha4beta1 and beta7 integrins; structure in first source
bio 1211BIO 1211: integrin alpha4beta1 inhibitor; structure in first source