Related Experiment Video

Updated: Jun 8, 2026

"Phagosome Closure Assay" to Visualize Phagosome Formation in Three Dimensions Using Total Internal Reflection Fluorescent Microscopy (TIRFM)
10:07

"Phagosome Closure Assay" to Visualize Phagosome Formation in Three Dimensions Using Total Internal Reflection Fluorescent Microscopy (TIRFM)

Published on: August 26, 2016

The iNOS/Src/FAK axis is critical in Toll-like receptor-mediated cell motility in macrophages

Ming-Chei Maa1, Miao Ying Chang, Jiarung Li

  • 1Institute of Molecular Systems Biomedicine, China Medical University, Taichung, Taiwan, Republic of China. mcmaa@mail.cmu.edu.tw

Biochimica Et Biophysica Acta
|September 21, 2010
PubMed

Insights

The inducible nitric oxide synthase (iNOS)/Src/FAK pathway is crucial for macrophage movement. This pathway is activated by various Toll-like receptor (TLR) ligands, not just TLR4, highlighting its general role in innate immunity.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Toll-like receptors (TLRs) are key in innate immunity, recognizing pathogen molecules.
  • Previous work linked lipopolysaccharide (LPS)-induced macrophage motility to the iNOS/Src/FAK pathway.

Purpose of the Study:

  • To determine if the iNOS/Src/FAK pathway mediates macrophage mobilization triggered by TLR ligands other than TLR4.
  • To investigate the role of iNOS, Src, and FAK in macrophage responses to TLR2, TLR3, and TLR9 agonists.

Main Methods:

  • Macrophages were stimulated with peptidoglycan (PGN, TLR2), polyinosinic-polycytidylic acid (polyI:C, TLR3), and CpG-oligodeoxynucleotides (CpG, TLR9).
  • Cell motility, Src and FAK activation (FAK Pi-Tyr861), and iNOS expression were analyzed.
  • Gene silencing (siRNA) and knockout models (iNOS-deficient) were employed.

Main Results:

  • PGN, polyI:C, and CpG stimulation increased macrophage motility and Src activation, similar to LPS.
  • Src and FAK were essential for PGN-, polyI:C-, and CpG-induced cell movement.
  • Macrophage mobility and associated signaling in response to these TLR ligands were significantly impaired in iNOS-deficient cells.

Conclusions:

  • The iNOS/Src/FAK signaling axis is a conserved mechanism for macrophage locomotion upon engagement of multiple TLRs.
  • This pathway plays a central role in innate immune cell migration triggered by diverse pathogen-associated molecular patterns.

More Related Videos

Time-lapse Imaging of Mouse Macrophage Chemotaxis09:33

Time-lapse Imaging of Mouse Macrophage Chemotaxis

Published on: April 2, 2020

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...
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
The Role of Actin and Myosin in Non-muscle Cells01:10

The Role of Actin and Myosin in Non-muscle Cells

Actin and myosin or actomyosin filaments also play a significant role in cells other than those involved in muscle contraction (which occurs within the sarcomere of muscle cells). The mechanism of non-muscle cell contractile bundles was first observed in Dictyostelium and Acanthamoeba. In non-muscle cells, two bundles are commonly found: stress fibers and actomyosin adherence belts. These contractile bundles are smaller and less organized than the ones found in muscle cells. They  are held...
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...
Cytoskeletal Coordination in Cell Migration01:32

Cytoskeletal Coordination in Cell Migration

A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker proteins that...
Role of Myosin in Cell Migration01:18

Role of Myosin in Cell Migration

Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
Myosin II  is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction. It is...