Gelsolin expression increases β1 -integrin affinity and L1210 cell adhesion.

Integrins are functionally regulated by "inside-out" signaling, in that stimulus-induced signaling pathways act on the intracellular integrin tail to regulate the activity of the receptor on the outside. Both a change in conformation (affinity) and clustering (avidity/valency) of the receptors occurs, but the mechanisms that regulate inside out signaling are not completely understood. Previously, we identified gelsolin in a proteomics screen to identify proteins involved in inside-out control of integrins using the lymphocytic leukemia cell line L1210. Furthermore, we showed that gelsolin was involved in affinity regulation of β1 -integrins in the leukemic cell line U937. Here, we examined how gelsolin regulates β1 -integrin affinity in the leukemia cell line L1210. We show that gelsolin is mainly expressed at the cell membrane and is present near β1 -integrins. The role for actin polymerization in integrin affinity regulation was examined using the actin modulating agent jasplakinolide, which decreased β1 -integrin affinity. Similarly, knock-down of gelsolin in L1210 cells also decreased β1 -integrin affinity and cell adhesion to collagen. These data suggest that increased actin polymerization through gelsolin regulates β1 -integrin affinity and cell adhesion.