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The molecular interaction of CAR and JAML recruits the central cell signal transducer PI3K

Petra Verdino1, Deborah A Witherden, Wendy L Havran

  • 1Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Science (New York, N.Y.)
|September 4, 2010
PubMed

Insights

The Coxsackie and adenovirus receptor (CAR) interacts with junctional adhesion molecule-like protein (JAML), revealing new roles in immunity and inflammation. This interaction is key for cell signaling, impacting diseases like asthma and cancer.

Area of Science:

  • Molecular and Cellular Biology
  • Immunology
  • Structural Biology

Background:

  • The Coxsackie and adenovirus receptor (CAR) is essential for coxsackievirus and adenovirus entry, and critical for adenoviral gene therapy.
  • Junctional adhesion molecule-like protein (JAML) interacts with CAR, highlighting its significance in immune responses, inflammation, and tissue maintenance.

Purpose of the Study:

  • To elucidate the structural basis of the JAML-CAR interaction.
  • To understand the functional consequences of JAML-CAR complex formation in cell signaling.

Main Methods:

  • X-ray crystallography was used to determine the structures of JAML ectodomain and its complex with CAR.
  • Biochemical assays and mutagenesis studies were performed to investigate the recruitment of phosphoinositide 3-kinase (P13K).

Main Results:

  • Crystal structures revealed an unusual immunoglobulin-domain assembly for JAML and a specific charged interface with CAR.
  • CAR-mediated clustering of JAML facilitates the recruitment of P13K via an intracellular motif, similar to the CD28 receptor.

Conclusions:

  • CAR and JAML function as crucial cell signaling receptors within the immune system.
  • The CAR-JAML interaction has potential implications for treating diseases such as asthma, cancer, and chronic wounds.

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