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Updated: Jan 10, 2026

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NDR1/2 kinases regulate cell polarization and cell motility through Cdc42 GTPase and Pard3 signaling in mammalian

Jun Gu1, Jelena Marjanovic2, Marjana Tomic-Canic2

  • 1Department of Molecular and Cellular Pharmacology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.

Biorxiv : the Preprint Server for Biology
|November 24, 2025
PubMed

Insights

Nuclear dbf2-related (NDR) kinases are crucial for cell migration and wound healing. These kinases regulate cell shape, motility, and polarization by controlling Cdc42 GTPase and Pard3 signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cell polarity and directed migration are essential for wound healing.
  • Nuclear dbf2-related (NDR) kinase pathways are conserved and involved in cell morphogenesis.

Purpose of the Study:

  • To investigate the role of NDR1/2 kinases in cell migration, polarization, and wound healing.
  • To elucidate the molecular mechanisms by which NDR kinases regulate these processes.

Main Methods:

  • RNA interference (RNAi) to knockdown NDR1/2 kinases.
  • Cell migration and wound healing assays.
  • Analysis of actin cytoskeleton, Cdc42 GTPase activity, and Pard3 localization.
  • Phosphorylation site analysis and rescue experiments.

Main Results:

  • NDR1/2 knockdown altered cell size, shape, actin cytoskeleton, and impaired migration persistence and polarization.
  • NDR kinases regulate Cdc42 GTPase dynamics and Pard3 subcellular localization.
  • NDR kinases phosphorylate Pard3 at Serine144; Pard3 overexpression partially restored wound healing.
  • NDR1 knockdown impaired ex vivo human skin wound closure.

Conclusions:

  • NDR kinases are critical regulators of cell motility and polarization.
  • NDR kinases control cell migration via Pard3 and Cdc42 signaling pathways.
  • NDR kinases play a significant physiological role in human wound healing.

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