Molecular mapping of KCNE4-dependent regulation of Kv1.3
2024; American Physical Society; Volume: 327; Issue: 6 Linguagem: Inglês
10.1152/ajpcell.00499.2024
ISSN1522-1563
AutoresDaniel Sastre, Magalí Colomer-Molera, Sara R. Roig, Ángela de Benito-Bueno, Paula G. Socuéllamos, Gregorio Fernández‐Ballester, Carmen Valenzuela, Antônio Felipe,
Tópico(s)Viral Infections and Immunology Research
ResumoThe voltage-gated potassium channel Kv1.3 plays a crucial role in the immune system response. In leukocytes, the channel is co-expressed with the dominant negative regulatory subunit KCNE4, which associates with Kv1.3 to trigger intracellular retention and accelerate C-type inactivation of the channel. Previous research has demonstrated that the main association between these proteins occurs through both COOH-termini. However, these data fail to fully elucidate the KCNE4-dependent modulation of channel kinetics. In the present study, we analyzed the contribution of each KCNE4 domain to the modulation of Kv1.3. Our results further confirmed that the COOH-terminus of KCNE4 is the main determinant involved in the association-triggered intracellular retention of the channel. In addition, interactions throughout the transmembrane region were also observed. Both the COOH-terminus and, especially, the transmembrane domain of KCNE4 accentuated the C-type inactivation of Kv1.3. Our data provide, for the first time, the molecular effects that a KCNE peptide, such as KCNE4, exerts on a
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