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Adhesion signaling - crosstalk between integrins, Src and Rho
Stephan Huveneers1, Erik H J Danen
1Division of Toxicology, Leiden Amsterdam Center for Drug Research, Leiden University, 2300 RA Leiden, The Netherlands. e.danen@lacdr.leidenuniv.nl
Journal of Cell Science
|April 3, 2009
Summary
Cellular behavior is controlled by interactions between cells and the extracellular matrix. This study explores the crosstalk between integrins, Src-family kinases, and Rho-family GTPases in cell adhesion and migration.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cell-extracellular matrix interactions are crucial for cellular behavior and signaling.
- Integrins sense matrix properties, influencing cytoskeleton organization and downstream signaling.
- Crosstalk between integrins, Src-family kinases, and Rho-family GTPases is central to adhesion signaling.
Purpose of the Study:
- To review recent advances in understanding the dynamic regulation of molecular connections between integrins, Src-family kinases, and Rho-family GTPases.
- To discuss the role of this signaling network in regulating cellular processes relevant to normal tissue function and disease.
Main Methods:
- This is a commentary, not an experimental study.
- Literature review and synthesis of recent findings.
Main Results:
- Extensive crosstalk exists between integrins, Src-family kinases, and Rho-family GTPases.
- This signaling network dynamically regulates molecular connections.
- The network influences cell adhesion, spreading, migration, and mechanotransduction.
Conclusions:
- Understanding the dynamic regulation of integrin-Src-Rho signaling is key to comprehending cellular processes.
- Dysregulation of this network contributes to various diseases.
- Further research into this signaling nexus holds potential for therapeutic interventions.
Related Concept Videos
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
01:10Integrins
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
01:15Activation of Integrins
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
01:30Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
01:03Anchoring Junctions
Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...