Bidirectional Transmembrane Signaling by Cytoplasmic Domain Separation in Integrins

Speaker : 蔡明怡

Commentator : 周楠華  醫師

Time: 2004/01/07  pm 2:00-3:00    Place: Room 601

Abstract:

    Integrins expressed on plasma membrane mediate the cellular adhesion to other cells or to extracellular matrix. This molecular function is critical for development, immune responses, wound healing, inflammation, and metastasis. Integrins use both "inside-out" and "outside-in" signaling to regulate their adhsiveness and interact with other molecules. Based on previous studies, introduction of an artificial clasp between the α and βcytoplasmic domains constrains an integrin to be inactive¹; whereas release of the clasp induces constitutive activation. The interaction between α and β cytoplasmic domains thus has been widely speculated to be important for integrin activation. However, this has never been directly demonstrated in living cells. Here, the authors used fluorescence resonance energy transfer (FRET) technique to investigate the spatial proximity of α and β cytoplasmic domains in leukocytes. They generatedα_L-mCFP/β₂-mYFP constructs for experiments. The authors found that ligand binding to LFA-1 (outside-in) and LFA-1 stimulating by chemokine receptors (inside-out) both can induce spatial separation of LFA-1 cytoplasmic domains. Thus, bidirection integrin signaling is accomplished by coupling extracellular conformational changes to separation of theα and β cytoplasmic domains, a distinctive mechanism for transmitting information across the plasma membrane.

Reference:

1.    Chafen Lu, et al.2001. Association of the Membrane Proximal Regions of the α and β Subunit Cytoplasmic Domains Constrains an Integrin in the Inactive State. J. Biol. Chem. 276,14642.

2.    Minsoo Kim, et al.2003. Bidirectional Transmembrane Signaling by Cytoplasmic Domain Separation in Integrins. SIENCE.301: 1720-1725.