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Coordination among cytoskeletal organization, cell contraction, and extracellular matrix development is dependent on

Rohtem Aviram1, Shelly Zaffryar-Eilot1, Anna Kaganovsky1

  • 1Department of Genetics and Developmental Biology, The Rappaport Faculty of Medicine and Research Institute, Technion - Israel Institute of Technology, Haifa, Israel.

The FEBS Journal
|December 5, 2024
PubMed

Insights

Lysyl oxidase (LOX) is crucial for vascular smooth muscle cell function. Its deletion disrupts cytoskeletal organization and contraction, contributing to aneurysm development.

Area of Science:

  • Vascular Biology
  • Biochemistry
  • Cell Biology

Background:

  • Aneurysm formation involves cellular pathways affecting intracellular machinery and extracellular matrix (ECM) deposition.
  • Lysyl oxidase (LOX), a secreted ECM-modifying enzyme, is implicated in aneurysm pathology in humans and mice.
  • LOX is highly expressed in medial vascular smooth muscle cells.

Purpose of the Study:

  • To investigate the role of lysyl oxidase (LOX) in smooth muscle cells during aneurysm development.
  • To dissect the mechanisms by which LOX influences cellular function and extracellular matrix organization.

Main Methods:

  • Conditional deletion of the Lox gene in smooth muscle cells.
  • Cell culture assays to analyze intracellular mechanisms.
  • In vivo analyses to assess cytoskeletal organization and cell contraction.

Main Results:

  • Lox deletion in smooth muscle cells led to loss of cytoskeletal organization.
  • LOX plays a cell-autonomous role in regulating myosin light-chain phosphorylation and cytoskeletal assembly.
  • Irregular smooth muscle contraction was observed following Lox deletion.

Conclusions:

  • LOX has novel intracellular functions beyond ECM modification.
  • LOX coordinates ECM development, cytoskeletal organization, and cell contraction.
  • LOX is essential for medial vascular development and function, and its dysregulation contributes to aneurysm formation.
Keywords:
aneurysmcytoskeletonextracellular matrixlysyl oxidasesmooth muscle cell

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