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13:52
Efficient Production and Purification of Recombinant Murine Kindlin-3 from Insect Cells for Biophysical Studies
Published on: March 19, 2014
Kindlins: essential regulators of integrin signalling and cell-matrix adhesion
Hannu Larjava1, Edward F Plow, Chuanyue Wu
1Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada.
EMBO Reports
|November 11, 2008
Summary
Kindlins are essential cytoplasmic proteins that regulate cell-extracellular matrix adhesion by controlling integrin activity. Their loss severely impacts cell behavior, leading to developmental defects and diseases like Kindler syndrome.
Area of Science:
- Cell Biology
- Biochemistry
- Developmental Biology
Background:
- Integrin-mediated cell-extracellular matrix (ECM) adhesion is crucial for cell behavior.
- Precise control of integrin ligand-binding affinity and spatial organization is necessary for proper cell-ECM adhesion.
- The regulation of integrins remains incompletely understood.
Purpose of the Study:
- To elucidate the role of kindlins in integrin signaling and cell-ECM adhesion.
- To understand how kindlins cooperate with other proteins in regulating cell behavior.
Main Methods:
- The study focuses on the function and interactions of kindlins within the cell-ECM adhesion complex.
- Investigated the consequences of kindlin loss on integrin signaling and cytoskeletal organization.
Main Results:
- Kindlins directly bind to beta-integrin cytoplasmic tails and work with talin for integrin activation.
- Kindlins interact with migfilin and integrin-linked kinase, promoting cytoskeletal reorganization.
- Loss of kindlins results in significant defects in integrin signaling, cell-ECM adhesion, and cytoskeletal organization.
Conclusions:
- Kindlins are essential for regulating integrin signaling and cell-ECM adhesion.
- Kindlin deficiency leads to severe developmental defects, including embryonic and postnatal lethality, and human diseases like Kindler syndrome.
- Kindlins, along with other integrin-proximal proteins, are vital for maintaining cellular integrity and function.
Related Concept Videos
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,...
01:17Intracellular 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...
01:15Activation 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.
01:24Overview of Cell-Matrix Interactions
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
00:55Laminins are the Adhesive Proteins of Basal Lamina
Laminins are heterotrimeric proteins with high molecular mass found in the extracellular matrix. Each laminin molecule is composed of three chains, viz. alpha, beta, and gamma, coded by five, four, and three paralogous genes, respectively. Laminins are categories based on the compositions of the three chains.
In humans, the five forms of alpha chains are LAMA 1, LAMA 2, LAMA 3, LAMA 4, and LAMA 5. The four forms of beta chains are LAMB 1, LAMB 2, LAMB 3, and LAMB 4. The three forms of gamma...
In humans, the five forms of alpha chains are LAMA 1, LAMA 2, LAMA 3, LAMA 4, and LAMA 5. The four forms of beta chains are LAMB 1, LAMB 2, LAMB 3, and LAMB 4. The three forms of gamma...
01:09Cytoskeletal Linker Proteins - Plakins
Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...