Gelsolin expression increases β₁‐integrin affinity and L1210 cell adhesion

Abstract

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.

Gelsolin-mediated activation of PI3K/Akt pathway is crucial for hepatocyte growth factor-induced cell scattering in gastric carcinoma

“…Our initial in vitro data revealed a decrease in invasiveness and loss of cellular aggregation upon gelsolin depletion in GC cells. This is corroborated by previous reports that gelsolin is required for tumor cell invasion and cellular aggregation in various carcinomas [ 33 , 46 , 47 ]. Since the effect of gelsolin on cellular aggregation is determinant upon the presence of functional E-cadherin, we investigated the possible effects of gelsolin on E-cadherin expression.…”

“…Furthermore, in contrast to its role in invasion and migration, the role of gelsolin in intercellular adhesion is not well studied. Gelsolin was previously reported to interfere with intercellular adhesion in canine kidney cells [ 29 ] and also in the regulation of β1-integrin affinity and cell adhesion in leukemic cells [ 33 ]. In this study we showed that gelsolin inhibits intercellular adhesion in GC cells by regulating the expression of E-cadherin.…”

Neutrophil integrin affinity regulation in adhesion, migration, and bacterial clearance

“…[14][15][16] Recently, it was shown that the protein level of gelsolin, an actin severing and capping protein, affects β 1 -integrin affinity and cell adhesion in the lymphocytic leukemia cell line L1210 and histiocytic lymphoma cell line U937. 17,18 As detected by 2D-gel electrophoresis, adherent growing L1210 cells (L1210-A) with active β 1 -integrins contained an almost 4-fold increase in gelsolin protein level compared with suspension growing L1210 cells (L1210-S) with inactive β 1 -integrins. 18 Further evidence that gelsolin protein levels were related to β 1 -integrin affinity regulation was obtained by modulating the protein levels in L1210 cells.…”

“…Knockdown of gelsolin in L1210-A cells or ectopic overexpression of gelsolin in L1210-S cells decreased or increased high affinity β 1 -integrins, respectively. 17 The severing and capping activity of gelsolin is controlled by binding of Ca 2+ and PI(4,5)P2. 19 Since gelsolin protein levels by itself affect β 1 -integrin affinity, without the need to stimulate the cells, it was hypothesized that gelsolin has basal activity, which accounts for the necessary actin severing and capping activity in resting cells.…”

Extracellular Vesicles in the Adaptive Process of Prostate Cancer during Inhibition of Androgen Receptor Signaling by Enzalutamide

“…Both THBS1 and GSN can directly bind ITGB1 (CD29) . The exosomal integrins have been reported to direct uptake of exosomes by specific organs, where exosomal integrin α6β1 is associated with lung metastasis in a breast cancer model .…”