title: LSm4 associates with the plasma membrane and acts as a co-factor in cell volume regulation.
abstract: ICln is a ubiquitous, multifunctional protein with functions in cell volume regulation and RNA processing, and is thus part of an intricate protein network critically involved in the homoeostasis of cells. To better understand this vital protein network in health and disease it is fundamental to characterize the interactions between the physiological pathways in which ICln is involved, as well as the spatio-temporal regulation of these interactions. In this study, we focused on the interaction between the two best studied pathways in which ICln is involved--regulatory volume decrease and RNA processing--and asked, whether or not the RNA processing factor and ICln interaction partner LSm4 may also have a function in cell volume regulation in NIH3T3 fibroblasts or HEK293 Phoenix cells. To address this question, we studied in isotonic and hypotonic conditions by FRET, biochemistry and electrophysiology, the intracellular distribution of the RNA processing factor LSm4, its interaction with ICln, as well as the involvement of LSm4 in the activation of the swelling dependent anion and osmolyte channel IClswell. In isotonic conditions, LSm4 associates with ICln, and the plasma membrane. Hypotonic cell swelling leads to the dissociation of LSm4 from the plasma membrane, and from ICln. Over-expression of LSm4 affects the translocation of ICln to the cell membrane and markedly inhibits the activation kinetics and current density of IClswell. These findings indicate that LSm4 not only acts in RNA processing, but also as a co-factor in cell volume regulation.
authors.affiliation: Department of Physiology and Medical Physics, Division of Physiology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gandini
authors.forename: Silvia
authors.initials: S
authors.lastname: Dossena
authors.forename: Valeria
authors.initials: V
authors.lastname: Vezzoli
authors.forename: Margherita
authors.initials: M
authors.lastname: Tamplenizza
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Salvioni
authors.forename: Markus
authors.initials: M
authors.lastname: Ritter
authors.forename: Markus
authors.initials: M
authors.lastname: Paulmichl
authors.forename: Johannes
authors.initials: J
authors.lastname: Furst
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D048429:Cell Size; D006801:Humans; D007038:Hypotonic Solutions / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D007552:Isotonic Solutions / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D021381:Protein Transport; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism*
chemical_list: C410035:CLNS1A protein, human; D007038:Hypotonic Solutions; D007473:Ion Channels; D007552:Isotonic Solutions; C485751:LSM4 protein, human; D017411:Ribonucleoproteins, Small Nuclear