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Comment
. 2009 Mar;15(3):249-50.
doi: 10.1038/nm0309-249.

When integrins fail to integrate

Andrés Hidalgo, Paul S Frenette
Comment

When integrins fail to integrate

Andrés Hidalgo et al. Nat Med. 2009 Mar.
No abstract available

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Figures

Figure 1
Figure 1
In healthy individuals, integrin activation in leukocytes and platelets is induced by extracellular stimuli through G protein-coupled receptors (GPCR) and transduced by the CalDAG-GEF1 and Rap1 pathway, which triggers the binding of a complex containing activated Rap1, Rap1-GTP–interacting adaptor molecule (RIAM), and Talin to NxxY/F motifs within the cytoplasmic tail of the β integrin chain. This allows the switch from low (inactive, bent form) to high affinity conformation (active, extended form) of integrins, mediating leukocyte arrest or platelet aggregation in inflamed or injured vessels (left). Kindlin-3 also binds to NxxY/F motifs, and in its absence, leukocyte and platelet integrins remain in low affinity conformation (LAD1-variant / LAD3, right). Kindlin-3 was clearly identified by three independent studies in this issue as the molecular basis of the known cases of LAD1-variant / LAD3. Nonetheless it remains possible that defects in other molecules involved in the inside-out integrin activation cascade, such asCalDAG-GEF1l, could produce a similar syndrome.
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