title: HERG K+ channels activation during beta(1) integrin-mediated adhesion to fibronectin induces an up-regulation of alpha(v)beta(3) integrin in the preosteoclastic leukemia cell line FLG 29.1.
abstract: Integrin receptors have been demonstrated to mediate either "inside-to-out" and "outside-to-in" signals, and by this way are capable of regulating many cellular functions, such as cell growth and differentiation, cell migration, and activation. Among the various integrin-centered signaling pathways discovered so far, we demonstrated that the modulation of the electrical potential of the plasma membrane (V(REST)) is an early integrin-mediated signal, which is related to neurite emission in neuroblastoma cells. This modulation is sustained by the activation of HERG K(+) channels, encoded by the ether-à-go-go-related gene (herg). The involvement of integrin-mediated signaling is being discovered in the hemopoietic system: in particular, osteoclasts are generated as well as induced to differentiate by interaction of osteoclast progenitors with the stromal cells, through the involvement of integrin receptors. We studied the effects of cell interaction with the extracellular matrix protein fibronectin (FN) in a human leukemic preosteoclastic cell line (FLG 29.1 cells), which has been demonstrated to express HERG currents. We report here that FLG 29.1 cells indeed adhere to purified FN through integrin receptors, and that this adhesion induces an osteoclast phenotype in these cells, as evidenced by the appearance of tartrate-resistant acid phosphatase, as well as by the increased expression of CD51/alpha(v)beta(3) integrin and calcitonin receptor. An early activation of HERG current (I(HERG)), without any increase in herg RNA or modifications of HERG protein was also observed in FN-adhering cells. This activation is apparently sustained by the beta(1) integrin subunit activation, through the involvement of a pertussis-toxin sensitive G(i) protein, and appears to be a determinant signal for the up-regulation of alpha(v)beta(3) integrin, as well as for the increased expression of calcitonin receptor.
authors.affiliation: Department of Experimental Pathology and Oncology, University of Firenze, Viale G. B. Morgagni, 50, 50134 Florence, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Hofmann
authors.forename: P A
authors.initials: PA
authors.lastname: Bernabei
authors.forename: O
authors.initials: O
authors.lastname: Crociani
authors.forename: A
authors.initials: A
authors.lastname: Cherubini
authors.forename: L
authors.initials: L
authors.lastname: Guasti
authors.forename: S
authors.initials: S
authors.lastname: Pillozzi
authors.forename: E
authors.initials: E
authors.lastname: Lastraioli
authors.forename: S
authors.initials: S
authors.lastname: Polvani
authors.forename: B
authors.initials: B
authors.lastname: Bartolozzi
authors.forename: V
authors.initials: V
authors.lastname: Solazzo
authors.forename: L
authors.initials: L
authors.lastname: Gragnani
authors.forename: P
authors.initials: P
authors.lastname: Defilippi
authors.forename: B
authors.initials: B
authors.lastname: Rosati
authors.forename: E
authors.initials: E
authors.lastname: Wanke
authors.forename: M
authors.initials: M
authors.lastname: Olivotto
authors.forename: A
authors.initials: A
authors.lastname: Arcangeli
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D027682:Cation Transport Proteins; D002448:Cell Adhesion; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D004553:Electric Conductivity; D051638:Ether-A-Go-Go Potassium Channels; D005353:Fibronectins / Q000378:metabolism*; D000091344:Filaggrin Proteins; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology / Q000502:physiology*; D007938:Leukemia; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000096:biosynthesis; D018003:Receptors, Calcitonin / Q000096:biosynthesis / Q000235:genetics; D019030:Receptors, Vitronectin / Q000096:biosynthesis / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000717249:FLG protein, human; D005353:Fibronectins; D000091344:Filaggrin Proteins; D019012:Integrin beta1; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D018003:Receptors, Calcitonin; D019030:Receptors, Vitronectin; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG