A novel role for integrin-linked kinase in epithelial sheet morphogenesis

Alisa Vespa1, Sudhir J A D'Souza, Lina Dagnino

  • 1Department of Physiology and Pharmacology and Regulatory Biology and Functional Genomics Research Group, Siebens-Drake Research Institute, London, Ontario N6A 5C1, Canada.

Insights

Integrin-linked kinase (ILK) is crucial for epithelial cell-cell adhesion, independent of its known role in cell migration. ILK

Area of Science:

  • Cell Biology
  • Epithelial Biology
  • Molecular Biology

Background:

  • Integrin-linked kinase (ILK) is a protein known for its role in cell motility and interactions with the extracellular matrix.
  • ILK is typically found in focal adhesions within undifferentiated epidermal keratinocytes.
  • Keratinocyte differentiation, induced by calcium (Ca2+), leads to cell-cell junction formation and altered ILK distribution.

Purpose of the Study:

  • To investigate the role of ILK in the formation of cell-cell junctions during keratinocyte differentiation.
  • To determine if ILK's function extends beyond integrin-mediated adhesion.

Main Methods:

  • Studied the translocation of ILK and adherens junction (AJ) proteins (E-cadherin, beta-catenin) in keratinocytes upon Ca2+ treatment.
  • Utilized an ILK deletion mutant (ILK 191-452) that cannot localize to the cell membrane to assess its impact on cell-cell adhesion.
  • Observed the formation of tight junctions (TJ) and epithelial sheet formation in cells expressing the ILK mutant.

Main Results:

  • Ca2+ treatment rapidly induced the translocation of AJ proteins (E-cadherin, beta-catenin) to the cell membrane, followed by TJ proteins.
  • ILK's movement kinetics mirrored that of AJ components, suggesting a role in early cell-cell contact formation.
  • Expression of a non-membrane-localizing ILK mutant (ILK 191-452) inhibited E-cadherin/beta-catenin translocation, preventing AJ and TJ formation, and disrupting epithelial sheet formation.

Conclusions:

  • ILK plays a novel and essential role in establishing epithelial cell-cell adhesion.
  • This function of ILK is distinct from its established role in integrin-mediated adhesion and cell migration.
  • ILK is critical for the proper formation and maintenance of adherens and tight junctions in epithelial cells.

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular 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...
Activation of Integrins01:15

Activation 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.
Integrins01:10

Integrins

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,...
Anchoring Junctions01:03

Anchoring 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:...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
Overview of Cell-Matrix Interactions01:24

Overview 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...