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AF6 negatively regulates Rap1-induced cell adhesion

Zhongchun Zhang1, Holger Rehmann, Leo S Price

  • 1Department of Physiological Chemistry and Centre of Biomedical Genetics, University Medical Centre, Utrecht 3508 AB, The Netherlands.

The Journal of Biological Chemistry
|July 30, 2005
PubMed

Insights

AF6 negatively regulates T cell adhesion by binding RapGTP, preventing its interaction with other proteins. This action helps maintain T cells in a non-adherent state.

Area of Science:

  • Cellular biology
  • Immunology
  • Molecular biology

Background:

  • AF6 protein links membrane proteins to the actin cytoskeleton.
  • AF6 interacts with Ras-like small GTPases, potentially acting as an effector for Ras and Rap.
  • Rap1 GTPase plays a crucial role in regulating integrin-mediated T cell adhesion.

Purpose of the Study:

  • To investigate the role of AF6 in Rap1-induced T cell adhesion.
  • To elucidate the mechanism by which AF6 influences Rap1 signaling.
  • To determine if AF6 acts as a positive or negative regulator of Rap1-mediated adhesion.

Main Methods:

  • RNA interference (RNAi) to knock down AF6 expression in T cells.
  • Overexpression of AF6 in T cells.
  • Assessment of Rap1-induced integrin-mediated cell adhesion.
  • Measurement of RapGTP levels.

Main Results:

  • Knockdown of AF6 enhanced Rap1-induced T cell adhesion, while AF6 overexpression inhibited it.
  • AF6-mediated inhibition of adhesion correlated with increased RapGTP levels.
  • Protein KIAA1849, also interacting with Rap1, did not affect Rap1-induced adhesion, highlighting AF6's specific role.

Conclusions:

  • AF6 acts as a negative regulator of Rap1-induced cell adhesion in T cells.
  • AF6 likely inhibits adhesion by sequestering RapGTP, preventing its interaction with downstream effectors and GTPase-activating proteins.
  • AF6 may function to buffer RapGTP in resting T cells, maintaining a non-adherent state.

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