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Updated: Jul 1, 2026

Quantitative Analysis of Cell Edge Dynamics during Cell Spreading
10:54

Quantitative Analysis of Cell Edge Dynamics during Cell Spreading

Published on: May 22, 2021

Discoidin domain receptor 1 activation suppresses alpha2beta1 integrin-dependent cell spreading through inhibition of

Yi-Chun Yeh1, Chau-Zen Wang, Ming-Jer Tang

  • 1Institute of Basic Medical Sciences, National Cheng-Kung University Medical College, Tainan, Taiwan, Republic of China.

Journal of Cellular Physiology
|September 10, 2008
PubMed

Insights

Discoidin domain receptor 1 (DDR1) inhibits cell spreading by suppressing Cdc42 activation. This pathway involves alpha(2)beta(1) integrin and focal adhesion kinase (FAK), impacting kidney development and cancer progression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Discoidin domain receptor 1 (DDR1) is implicated in kidney development and cancer.
  • DDR1 overexpression inhibits cell spreading, a process vital for cell differentiation and survival.
  • The precise molecular mechanisms linking DDR1 to cell spreading remain largely unknown.

Purpose of the Study:

  • To elucidate the novel signaling pathway through which DDR1 regulates cell spreading in Mardin-Darby canine kidney (MDCK) cells.
  • To investigate the role of Rho-family GTPases, specifically Cdc42, in DDR1-mediated cell spreading.
  • To identify upstream regulators, including integrins and focal adhesion kinase (FAK), involved in this pathway.

Main Methods:

  • Assessed Rho-family GTPase activity in transfected MDCK cells.
  • Quantified cell spreading extent after transfecting with constitutively active or dominant-negative GTPases (Rac1, Cdc42, FAK).
  • Utilized alpha(2)beta(1) integrin blocking antibodies and ectopic/dominant-negative FAK expression to probe upstream signaling.

Main Results:

  • DDR1 overexpression decreased filamentous actin, Rac1, and Cdc42 activity, but not RhoA.
  • DDR1-inhibited cell spreading was rescued by constitutively active Cdc42, confirming Cdc42 dependence.
  • Collagen-induced Cdc42 activation is mediated by alpha(2)beta(1) integrin and enhanced by FAK.

Conclusions:

  • DDR1 activation inhibits cell spreading via suppression of alpha(2)beta(1) integrin-mediated Cdc42 activation.
  • This novel DDR1-Cdc42 signaling axis provides insights into cytoskeleton regulation and cell behavior.
  • Understanding this pathway could offer new therapeutic targets for kidney diseases and cancers.

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