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Identification of self through two-dimensional chemistry and synapses
M L Dustin1, S K Bromley, M M Davis
1Skirball Institute of Molecular Medicine, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA. dustin@saturn.med.nyu.edu
Annual Review of Cell and Developmental Biology
|November 1, 2001
Summary
Immune and nervous system cells form informational synapses using distinct adhesion regimes. Differences in off-rates (k(off)) control signaling thresholds, revealing shared chemistry between systems.
Area of Science:
- Cellular biology
- Neuroscience
- Immunology
Background:
- Cells in the immune and nervous systems communicate via informational synapses.
- The two-dimensional (2D) chemistry of synapse formation is an emerging area of study.
Purpose of the Study:
- To explore the 2D chemistry of synapse formation.
- To gain biological insights from kinetic rates and equilibrium constants.
Main Methods:
- Fluorescence imaging techniques.
- Mechanical techniques for analysis.
- Analysis of 2D kinetic rates (k(on), k(off)) and equilibrium constants (K(d)).
Main Results:
- Identified two adhesion regimes: disordered (slow k(on)) and self-ordered (10^4-fold faster k(on)).
- 2D k(off) is similar to solution k(off) and relates more to intrinsic interaction properties than 2D k(on).
- Signaling thresholds can be set by differences in k(off).
- Early signaling complexes compartmentalize into synergistic signaling domains.
- Immune antigen receptor components play a role in neural synapse editing.
Conclusions:
- Significant parallels exist in informational synapse formation between immune and nervous systems.
- Common 2D chemistry and signaling strategies underlie these parallels.
- k(off) differences are crucial for setting signaling thresholds.
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