Kv1.3 and Kv1.5 channels in leukocytes

Author

Vallejo Gracia, Albert

Director

Felipe Campo, Antonio

Date of defense

2016-04-15

Pages

142 p.



Department/Institute

Universitat de Barcelona. Departament de Bioquímica i Biologia Molecular (Biologia)

Abstract

Voltage dependent potassium channels are a group of plasma membrane ion channels with a key role in the immune system as the predominant ion channels controlling the resting membrane potential and tuning intracellular Ca2+ signaling in lymphocytes, monocytes, macrophages, and dendritic cells. Leukocytes present a limited Kv repertoire, including Kv1.3 and Kv1.5 channel isoforms. Kv1.3 is expressed in the immune system, and the blockade of this channel is associated with selective inhibition of T cell activation and proliferation. A functional Kv channel is an oligomeric complex composed of pore-forming and ancillary subunits. The KCNE gene family (KCNE1-5) is a novel group of modulatory Kv channel elements expressed in several tissues including leukocytes. KCNE peptides are small single spanning membrane proteins known to modulate Kv channels trafficking and biophysical properties. The hypothesis of the present PhD thesis entitled “Kv1.3 and Kv1.5 channels in leukocytes” was that changes in the channelosome composition by modulating the heterooligomeric combinations of the Kv1.3 channelosome control physiological and neoplastic cell growth as well as leukocyte responses. Evidence suggests that Kv channels are involved in cell differentiation and cell cycle control (because non-specific drugs, such as 4-AP and TEA, impaire proliferation), and they are also known to be remodeled during carcinogenesis. Thus, we elucidated the role of Kv1.3 and Kv1.5 channels in cell growth and their relationship with cancer, in models such as B lymphocytes and lymphomas (non-Hodgkin lymphomas), pancreatic ductal adenocarcinoma (PDAC) and glioblastomas. In spite of its significance, the mechanisms that regulate Kv1.3 and its role in the T cell activation are not well known. To that end, we analyzed the expression of KCNEs ancillary subunits upon different states of activation and proliferation of leukocytes (macrophages, T and B lymphocytes). In addition, recent data from our laboratory demonstrate that KCNE4, acting as a dominant negative ancillary subunit, physically interacts with Kv1.3 inhibiting K+ currents and retaining the channel intracellularly. Therefore, we studied the Kv1.3 modulation by the auxiliary subunit KCNE4 in leukocytes.

Keywords

Leucòcits; Leucocitos; Leucocytes; Càncer; Cáncer; Cancer; Fisiologia cel·lular; Fisiología celular; Cell physiology; Canals de potassi; Canales de potasio; Potassium channels

Subjects

577 - Biochemistry. Molecular biology. Biophysics

Knowledge Area

Ciències Experimentals i Matemàtiques

Documents

AVG_THESIS.pdf

26.28Mb

 

Rights

ADVERTIMENT. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs.

This item appears in the following Collection(s)