2024-03-19T03:43:17Zhttps://www.tdx.cat/oai/requestoai:www.tdx.cat:10803/3977972017-08-30T00:10:12Zcom_10803_1col_10803_15
TDX (Tesis Doctorals en Xarxa)
author
Vallejo Gracia, Albert
authoremail
albertvallejo@hotmail.com
authoremailshow
false
director
Felipe Campo, Antonio
authorsendemail
true
2016-11-23T11:48:07Z
2017-04-15T05:45:11Z
2016-04-15
http://hdl.handle.net/10803/397797
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.
eng
Leucòcits
Leucocitos
Leucocytes
Càncer
Cáncer
Cancer
Fisiologia cel·lular
Fisiología celular
Cell physiology
Canals de potassi
Canales de potasio
Potassium channels
Kv1.3 and Kv1.5 channels in leukocytes
info:eu-repo/semantics/doctoralThesis info:eu-repo/semantics/publishedVersion
URL
https://www.tdx.cat/bitstream/10803/397797/1/AVG_THESIS.pdf
File
MD5
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application/pdf
AVG_THESIS.pdf