title: Functional K(v)10.1 channels localize to the inner nuclear membrane.
abstract: Ectopically expressed human K(V)10.1 channels are relevant players in tumor biology. However, their function as ion channels at the plasma membrane does not totally explain their crucial role in tumors. Both in native and heterologous systems, it has been observed that a majority of K(V)10.1 channels remain at intracellular locations. In this study we investigated the localization and possible roles of perinuclear K(V)10.1. We show that K(V)10.1 is expressed at the inner nuclear membrane in both human and rat models; it co-purifies with established inner nuclear membrane markers, shows resistance to detergent extraction and restricted mobility, all of them typical features of proteins at the inner nuclear membrane. K(V)10.1 channels at the inner nuclear membrane are not all transported directly from the ER but rather have been exposed to the extracellular milieu. Patch clamp experiments on nuclei devoid of external nuclear membrane reveal the existence of channel activity compatible with K(V)10.1. We hypothesize that K(V)10.1 channels at the nuclear envelope might participate in the homeostasis of nuclear K(+), or indirectly interact with heterochromatin, both factors known to affect gene expression.
authors.affiliation: Department of Molecular Biology of Neuronal Signals, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.forename: Araceli
authors.initials: A
authors.lastname: Sánchez
authors.forename: María E
authors.initials: ME
authors.lastname: Rubio
authors.forename: Tobias
authors.initials: T
authors.lastname: Kohl
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pardo
authors.forename: Walter
authors.initials: W
authors.lastname: Stühmer
mesh_terms: D000818:Animals; D016466:CHO Cells; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D051638:Ether-A-Go-Go Potassium Channels / Q000096:biosynthesis*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009685:Nuclear Envelope / Q000378:metabolism*; D018408:Patch-Clamp Techniques
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D007473:Ion Channels; C496884:KCNH1 protein, human; C496885:Kcnh1 protein, mouse