title: 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.
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Jeroen D
authors.initials: JD
authors.lastname: Langereis
authors.forename: Leo
authors.initials: L
authors.lastname: Koenderman
authors.forename: Anna
authors.initials: A
authors.lastname: Huttenlocher
authors.forename: Laurien H
authors.initials: LH
authors.lastname: Ulfman
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D018260:Gelsolin / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000172:deficiency / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis / Q000378:metabolism*; D007939:Leukemia L1210; D051379:Mice; D015398:Signal Transduction
chemical_list: D000199:Actins; D018260:Gelsolin; D019012:Integrin beta1
keywords: attachment; cell membrane; cytoskeleton; gelsolin; migration