Integrin-linked kinase interactions with ELMO2 modulate cell polarity

Ernest Ho1, Tames Irvine, Gregory J A Vilk

  • 1Department of Physiology and Pharmacology, Child Health Research Institute and Lawson Health Research Institute, University of Western Ontario, London, ON, Canada.

Insights

A newly discovered Integrin-linked kinase (ILK) complex with ELMO2 and RhoG is crucial for cell polarization and directed migration. This finding advances understanding of tissue development and repair.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cell polarization is vital for directed cell migration in development, regeneration, and metastasis.
  • Integrin-linked kinase (ILK) is essential for cell polarization, but its precise role in normal epithelia is unclear.

Purpose of the Study:

  • To elucidate the mechanisms by which ILK modulates cell polarization in normal epithelia.
  • To identify novel protein complexes involving ILK in cell polarization.

Main Methods:

  • Identification and characterization of a novel ILK protein complex.
  • Demonstration of RhoG presence within ILK-ELMO2 complexes.
  • Localization studies of the multiprotein complex in polarized cells.

Main Results:

  • A novel ILK complex containing Engulfment and Cell Motility 2 (ELMO2) and RhoG was identified.
  • This complex localizes to the leading lamellipodia of polarized cells.
  • RhoG binding to ELMO is critical for ILK-induced cell polarization; ILK and ELMO2 synergistically promote polarity and migration.

Conclusions:

  • The RhoG-ELMO2-ILK complex is essential for establishing cell polarity and directed migration.
  • ILK's ability to induce front-rear cell polarity is dependent on its interaction with ELMO2 and RhoG.

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...
Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
Mechanism of Lamellipodia Formation01:31

Mechanism of Lamellipodia Formation

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
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.
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:...
Cell Motility through Blebbing01:16

Cell Motility through Blebbing

Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...