A non-canonical di-acidic signal at the C-terminus of Kv1.3 determines anterograde trafficking and surface expression

Impairment of Kv1.3 expression at the cell membrane in leukocytes and sensory neuron contributes to the pathophysiology of autoimmune diseases and sensory syndromes. Molecular mechanisms underlying Kv1.3 channel trafficking to the plasma membrane remain elusive. We report a novel non-canonical di-acidic signal (E483/484) at the C-terminus of Kv1.3 essential for anterograde transport and surface expression. Notably, homologous motifs are conserved in neuronal Kv1 and Shaker channels. Biochemical analysis revealed interactions with the Sec24 subunit of the coat protein complex II. Disruption of this complex retains the channel at the endoplasmic reticulum. A molecular model of the Kv1.3-Sec24a complex suggests salt-bridges between the di-acidic E483/484 motif in Kv1.3 and the di-basic R750/752 sequence in Sec24. These findings identify a previously unrecognized motif of Kv channels essential for their expression on the cell surface. Our results contribute to our understanding of how Kv1 channels target to the cell membrane, and provide new therapeutic strategies for the treatment of pathological conditions

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19 : a multicentre, randomised, double-blind, non-inferiority phase IIb trial

A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with , . From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4 + and CD8 + T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19. Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. HIPRA SCIENTIFIC, S.L.U

Monitoring of chicken meat freshness by means of a colorimetric sensor array

A new optoelectronic nose to monitor chicken meat ageing has been developed. It is based on 16 pigments prepared by the incorporation of different dyes (pH indicators, Lewis acids, hydrogenbonding derivatives, selective probes and natural dyes) into inorganic materials (UVM-7, silica and alumina). The colour changes of the sensor array were characteristic of chicken ageing in a modi¿ed packaging atmosphere (30% CO2¿70% N2). The chromogenic array data were processed with qualitative (PCA) and quantitative (PLS) tools. The PCA statistical analysis showed a high degree of dispersion, with nine dimensions required to explain 95% of variance. Despite this high dimensionality, a tridimensional representation of the three principal components was able to differentiate ageing with 2-day intervals. Moreover, the PLS statistical analysis allows the creation of a model to correlate the chromogenic data with chicken meat ageing. The model offers a PLS prediction model for ageing with values of 0.9937, 0.0389 and 0.994 for the slope, the intercept and the regression coef¿cient, respectively, and is in agreement with the perfect ¿t between the predicted and measured values observed. The results suggest the feasibility of this system to help develop optoelectronic noses that monitor food freshness.Salinas Soler, Y.; Ros-Lis, JV.; Vivancos, J.; Martínez Mañez, R.; Marcos Martínez, MD.; Aucejo Romero, S.; Herranz, N.... (2012). Monitoring of chicken meat freshness by means of a colorimetric sensor array. Analyst. 137(16):3635-3643. doi:10.1039/C2AN35211GS3635364313716Anang, D. M., Rusul, G., Ling, F. H., & Bhat, R. (2010). Inhibitory effects of lactic acid and lauricidin on spoilage organisms of chicken breast during storage at chilled temperature. International Journal of Food Microbiology, 144(1), 152-159. doi:10.1016/j.ijfoodmicro.2010.09.014HINTON, A., & INGRAM, K. D. (2005). Microbicidal Activity of Tripotassium Phosphate and Fatty Acids toward Spoilage and Pathogenic Bacteria Associated with Poultry. Journal of Food Protection, 68(7), 1462-1466. doi:10.4315/0362-028x-68.7.1462Jeremiah, L. . (2001). Packaging alternatives to deliver fresh meats using short- or long-term distribution. Food Research International, 34(9), 749-772. doi:10.1016/s0963-9969(01)00096-5Ellis, D. I., & Goodacre, R. (2001). Rapid and quantitative detection of the microbial spoilage of muscle foods: current status and future trends. Trends in Food Science & Technology, 12(11), 414-424. doi:10.1016/s0924-2244(02)00019-5Vinci, G., & Antonelli, M. . (2002). Biogenic amines: quality index of freshness in red and white meat. Food Control, 13(8), 519-524. doi:10.1016/s0956-7135(02)00031-2Lovestead, T. M., & Bruno, T. J. (2010). Detection of poultry spoilage markers from headspace analysis with cryoadsorption on a short alumina PLOT column. Food Chemistry, 121(4), 1274-1282. doi:10.1016/j.foodchem.2010.01.044Bota, G. M., & Harrington, P. B. (2006). Direct detection of trimethylamine in meat food products using ion mobility spectrometry. Talanta, 68(3), 629-635. doi:10.1016/j.talanta.2005.05.001Grau, R., Sánchez, A. J., Girón, J., Iborra, E., Fuentes, A., & Barat, J. M. (2011). Nondestructive assessment of freshness in packaged sliced chicken breasts using SW-NIR spectroscopy. Food Research International, 44(1), 331-337. doi:10.1016/j.foodres.2010.10.011Sahar, A., Boubellouta, T., & Dufour, É. (2011). Synchronous front-face fluorescence spectroscopy as a promising tool for the rapid determination of spoilage bacteria on chicken breast fillet. Food Research International, 44(1), 471-480. doi:10.1016/j.foodres.2010.09.006Lin, M., Al-Holy, M., Mousavi-Hesary, M., Al-Qadiri, H., Cavinato, A. G., & Rasco, B. A. (2004). Rapid and quantitative detection of the microbial spoilage in chicken meat by diffuse reflectance spectroscopy (600-1100 nm). Letters in Applied Microbiology, 39(2), 148-155. doi:10.1111/j.1472-765x.2004.01546.xMartínez-Máñez, R., & Sancenón, F. (2003). Fluorogenic and Chromogenic Chemosensors and Reagents for Anions. Chemical Reviews, 103(11), 4419-4476. doi:10.1021/cr010421eAmendola, V., Fabbrizzi, L., & Mosca, L. (2010). Anion recognition by hydrogen bonding: urea-based receptors. Chemical Society Reviews, 39(10), 3889. doi:10.1039/b822552bQuang, D. T., & Kim, J. S. (2010). Fluoro- and Chromogenic Chemodosimeters for Heavy Metal Ion Detection in Solution and Biospecimens. Chemical Reviews, 110(10), 6280-6301. doi:10.1021/cr100154pAmendola, V., Bonizzoni, M., Esteban-Gómez, D., Fabbrizzi, L., Licchelli, M., Sancenón, F., & Taglietti, A. (2006). Some guidelines for the design of anion receptors. Coordination Chemistry Reviews, 250(11-12), 1451-1470. doi:10.1016/j.ccr.2006.01.006Chen, X., Zhou, Y., Peng, X., & Yoon, J. (2010). Fluorescent and colorimetric probes for detection of thiols. Chemical Society Reviews, 39(6), 2120. doi:10.1039/b925092aMohr, G. J. (2006). New chromogenic and fluorogenic reagents and sensors for neutral and ionic analytes based on covalent bond formation–a review of recent developments. Analytical and Bioanalytical Chemistry, 386(5), 1201-1214. doi:10.1007/s00216-006-0647-3Kerry, J. P., O’Grady, M. N., & Hogan, S. A. (2006). Past, current and potential utilisation of active and intelligent packaging systems for meat and muscle-based products: A review. Meat Science, 74(1), 113-130. doi:10.1016/j.meatsci.2006.04.024Rakow, N. A., & Suslick, K. S. (2000). A colorimetric sensor array for odour visualization. Nature, 406(6797), 710-713. doi:10.1038/35021028Lim, S. H., Kemling, J. W., Feng, L., & Suslick, K. S. (2009). A colorimetric sensor array of porous pigments. The Analyst, 134(12), 2453. doi:10.1039/b916571aPalacios, M. A., Nishiyabu, R., Marquez, M., & Anzenbacher, P. (2007). Supramolecular Chemistry Approach to the Design of a High-Resolution Sensor Array for Multianion Detection in Water. Journal of the American Chemical Society, 129(24), 7538-7544. doi:10.1021/ja0704784Wu, Y., Na, N., Zhang, S., Wang, X., Liu, D., & Zhang, X. (2009). Discrimination and Identification of Flavors with Catalytic Nanomaterial-Based Optical Chemosensor Array. Analytical Chemistry, 81(3), 961-966. doi:10.1021/ac801733kJanzen, M. C., Ponder, J. B., Bailey, D. P., Ingison, C. K., & Suslick, K. S. (2006). Colorimetric Sensor Arrays for Volatile Organic Compounds. Analytical Chemistry, 78(11), 3591-3600. doi:10.1021/ac052111sSuslick, B. A., Feng, L., & Suslick, K. S. (2010). Discrimination of Complex Mixtures by a Colorimetric Sensor Array: Coffee Aromas. Analytical Chemistry, 82(5), 2067-2073. doi:10.1021/ac902823wHuang, X., Xin, J., & Zhao, J. (2011). A novel technique for rapid evaluation of fish freshness using colorimetric sensor array. Journal of Food Engineering, 105(4), 632-637. doi:10.1016/j.jfoodeng.2011.03.034Anzenbacher, Jr., P., Lubal, P., Buček, P., Palacios, M. A., & Kozelkova, M. E. (2010). A practical approach to optical cross-reactive sensor arrays. Chemical Society Reviews, 39(10), 3954. doi:10.1039/b926220mRos-Lis, J. V., García, B., Jiménez, D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Valldecabres, M. C. (2004). Squaraines as Fluoro−Chromogenic Probes for Thiol-Containing Compounds and Their Application to the Detection of Biorelevant Thiols. Journal of the American Chemical Society, 126(13), 4064-4065. doi:10.1021/ja031987iRos-Lis, J. V., Martínez-Máñez, R., Rurack, K., Sancenón, F., Soto, J., & Spieles, M. (2004). Highly Selective Chromogenic Signaling of Hg2+in Aqueous Media at Nanomolar Levels Employing a Squaraine-Based Reporter. Inorganic Chemistry, 43(17), 5183-5185. doi:10.1021/ic049422qRos-Lis, J. V., Marcos, M. D., Mártinez-Máñez, R., Rurack, K., & Soto, J. (2005). A Regenerative Chemodosimeter Based on Metal-Induced Dye Formation for the Highly Selective and Sensitive Optical Determination of Hg2+ Ions. Angewandte Chemie International Edition, 44(28), 4405-4407. doi:10.1002/anie.200500583Ros-Lis, J. V., Martínez-Máñez, R., & Soto, J. (2005). Colorimetric Signaling of Large Aromatic Hydrocarbons via the Enhancement of Aggregation Processes. Organic Letters, 7(12), 2337-2339. doi:10.1021/ol050564dCliment, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., Rurack, K., & Amorós, P. (2009). The Determination of Methylmercury in Real Samples Using Organically Capped Mesoporous Inorganic Materials Capable of Signal Amplification. Angewandte Chemie International Edition, 48(45), 8519-8522. doi:10.1002/anie.200904243Ábalos, T., Jiménez, D., Martínez-Máñez, R., Ros-Lis, J. V., Royo, S., Sancenón, F., … Parra, M. (2009). Hg2+ and Cu2+ selective detection using a dual channel receptor based on thiopyrylium scaffoldings. Tetrahedron Letters, 50(27), 3885-3888. doi:10.1016/j.tetlet.2009.04.060Climent, E., Giménez, C., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., & Soto, J. (2011). Selective and sensitive chromo-fluorogenic sensing of anionic surfactants in water using functionalised silica nanoparticles. Chemical Communications, 47(24), 6873. doi:10.1039/c1cc11393cRoyo, S., Costero, A. M., Parra, M., Gil, S., Martínez-Máñez, R., & Sancenón, F. (2011). Chromogenic, Specific Detection of the Nerve-Agent Mimic DCNP (a Tabun Mimic). Chemistry - A European Journal, 17(25), 6931-6934. doi:10.1002/chem.201100602García-Acosta, B., Comes, M., Bricks, J. L., Kudinova, M. A., Kurdyukov, V. V., Tolmachev, A. I., … Amorós, P. (2006). Sensory hybrid host materials for the selective chromo-fluorogenic detection of biogenic amines. Chem. Commun., (21), 2239-2241. doi:10.1039/b602497aSancenón, F., Descalzo, A. B., Martínez-Máñez, R., Miranda, M. A., & Soto, J. (2001). A Colorimetric ATP Sensor Based on 1,3,5-Triarylpent-2-en-1,5-diones. Angewandte Chemie International Edition, 40(14), 2640-2643. doi:10.1002/1521-3773(20010716)40:143.0.co;2-aEsteban, J., Ros-Lis, J. V., Martínez-Máñez, R., Marcos, M. D., Moragues, M., Soto, J., & Sancenón, F. (2010). Sensitive and Selective Chromogenic Sensing of Carbon Monoxide by Using Binuclear Rhodium Complexes. Angewandte Chemie International Edition, 49(29), 4934-4937. doi:10.1002/anie.201001344Moragues, M. E., Esteban, J., Ros-Lis, J. V., Martínez-Máñez, R., Marcos, M. D., Martínez, M., … Sancenón, F. (2011). Sensitive and Selective Chromogenic Sensing of Carbon Monoxide via Reversible Axial CO Coordination in Binuclear Rhodium Complexes. Journal of the American Chemical Society, 133(39), 15762-15772. doi:10.1021/ja206251rRos-Lis, J. V., Martínez-Máñez, R., Sancenón, F., Soto, J., Rurack, K., & Weißhoff, H. (2007). Signalling Mechanisms in Anion-Responsive Push-Pull Chromophores: The Hydrogen-Bonding, Deprotonation and Anion-Exchange Chemistry of Functionalized Azo Dyes. European Journal of Organic Chemistry, 2007(15), 2449-2458. doi:10.1002/ejoc.200601111El Haskouri, J., Zárate, D. O. de, Guillem, C., Latorre, J., Caldés, M., Beltrán, A., … Amorós, P. (2002). Silica-based powders and monoliths with bimodal pore systemsElectronic supplementary information (ESI) available: UV–Vis spectrum of sample 3. See http://www.rsc.org/suppdata/cc/b1/b110883b/. Chemical Communications, (4), 330-331. doi:10.1039/b110883bDe Jong, S. (1993). SIMPLS: An alternative approach to partial least squares regression. Chemometrics and Intelligent Laboratory Systems, 18(3), 251-263. doi:10.1016/0169-7439(93)85002-xSmolander, M., Hurme, E., Latva-Kala, K., Luoma, T., Alakomi, H.-L., & Ahvenainen, R. (2002). Myoglobin-based indicators for the evaluation of freshness of unmarinated broiler cuts. Innovative Food Science & Emerging Technologies, 3(3), 279-288. doi:10.1016/s1466-8564(02)00043-7Dainty, R. H. (1996). Chemical/biochemical detection of spoilage. International Journal of Food Microbiology, 33(1), 19-33. doi:10.1016/0168-1605(96)01137-3De Fernando, G. D. G., Nychas, G. J. E., Peck, M. W., & Ordóñez, J. A. (1995). Growth/survival of psychrotrophic pathogens on meat packaged under modified atmospheres. International Journal of Food Microbiology, 28(2), 221-231. doi:10.1016/0168-1605(95)00058-5Descalzo, A. B., Dolores Marcos, M., Monte, C., Martínez-Máñez, R., & Rurack, K. (2007). Mesoporous silica materials with covalently anchored phenoxazinone dyes as fluorescent hybrid materials for vapour sensing. Journal of Materials Chemistry, 17(44), 4716. doi:10.1039/b707473eDescalzo, A. B., Rurack, K., Weisshoff, H., Martínez-Máñez, R., Marcos, M. D., Amorós, P., … Soto, J. (2005). Rational Design of a Chromo- and Fluorogenic Hybrid Chemosensor Material for the Detection of Long-Chain Carboxylates. Journal of the American Chemical Society, 127(1), 184-200. doi:10.1021/ja045683nComes, M., Aznar, E., Moragues, M., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., … Amorós, P. (2009). Mesoporous Hybrid Materials Containing Nanoscopic «Binding Pockets» for Colorimetric Anion Signaling in Water by using Displacement Assays. Chemistry - A European Journal, 15(36), 9024-9033. doi:10.1002/chem.200900890Nychas, G.-J. E., & Tassou, C. C. (1997). Spoilage Processes and Proteolysis in Chicken as Detected by HPLC. Journal of the Science of Food and Agriculture, 74(2), 199-208. doi:10.1002/(sici)1097-0010(199706)74:23.0.co;2-4Jiménez, S. M., Salsi, M. S., Tiburzi, M. C., Rafaghelli, R. C., Tessi, M. A., & Coutaz, V. R. (1997). Spoilage microflora in fresh chicken breast stored at 4 °C : influence of packaging methods. Journal of Applied Microbiology, 83(5), 613-618. doi:10.1046/j.1365-2672.1997.00276.xDe Fernando, G. D. G., Nychas, G. J. E., Peck, M. W., & Ordóñez, J. A. (1995). Growth/survival of psychrotrophic pathogens on meat packaged under modified atmospheres. International Journal of Food Microbiology, 28(2), 221-231. doi:10.1016/0168-1605(95)00058-5BALAMATSIA, C., PATSIAS, A., KONTOMINAS, M., & SAVVAIDIS, I. (2007). Possible role of volatile amines as quality-indicating metabolites in modified atmosphere-packaged chicken fillets: Correlation with microbiological and sensory attributes. Food Chemistry, 104(4), 1622-1628. doi:10.1016/j.foodchem.2007.03.013Balamatsia, C. C., Paleologos, E. K., Kontominas, M. G., & Savvaidis, I. N. (2006). Correlation between microbial flora, sensory changes and biogenic amines formation in fresh chicken meat stored aerobically or under modified atmosphere packaging at 4 °C: possible role of biogenic amines as spoilage indicators. Antonie van Leeuwenhoek, 89(1), 9-17. doi:10.1007/s10482-005-9003-4Smolander, M., Hurme, E., Latva-Kala, K., Luoma, T., Alakomi, H.-L., & Ahvenainen, R. (2002). Myoglobin-based indicators for the evaluation of freshness of unmarinated broiler cuts. Innovative Food Science & Emerging Technologies, 3(3), 279-288. doi:10.1016/s1466-8564(02)00043-7Dainty, R. H. (1996). Chemical/biochemical detection of spoilage. International Journal of Food Microbiology, 33(1), 19-33. doi:10.1016/0168-1605(96)01137-3Berrueta, L. A., Alonso-Salces, R. M., & Héberger, K. (2007). Supervised pattern recognition in food analysis. Journal of Chromatography A, 1158(1-2), 196-214. doi:10.1016/j.chroma.2007.05.02

Papel de las placas complejas de ateroma aórtico en la recurrencia del infarto cerebral de etiología incierta

Introducción y objetivos. En un subgrupo de pacientes con infarto cerebral, las exploraciones diagnósticas no invasivas no permiten establecer un diagnóstico etiológico. Hemos estudiado su evolución y el valor del ecocardiograma transesofágico en el diagnóstico del ateroma complejo aórtico en pacientes con infarto cerebral de etiología incierta que presentan recurrencia. Pacientes y método. Al evaluar a 1.840 pacientes consecutivos con un primer infarto cerebral mediante un protocolo restrictivo para la ecocardiografía transesofágica, en 248 no pudo establecerse un diagnóstico etiológico. Durante 1 año de seguimiento con fármacos antiplaquetarios, se practicó un ecocardiograma transesofágico en caso de nuevo episodio isquémico cerebral. Se comparó la prevalencia de placas complejas aórticas en estos pacientes con recurrencia respecto a la de los infartos cerebrales de etiología incierta del French Study of Aortic Plaques in Stroke que no presentaron un segundo infarto cerebral. Resultados. Presentaron un segundo infarto cerebral 17 de los 248 pacientes con etiología incierta (6,9%). El ecocardiograma transesofágico estableció la etiología en 15 de ellos (88,2%), que fue atribuida a placas complejas de ateroma aórtico en 14 casos (82,4%). En cambio, entre los pacientes del French Study con infarto cerebral de etiología incierta que no presentaron reinfarto cerebral durante el primer año de seguimiento, la prevalencia de placas complejas aórticas fue del 21,1% (p < 0,0001). Conclusiones. Durante el primer año de seguimiento con antiagregantes, la mayoría de los pacientes con infarto cerebral de etiología incierta no presenta recurrencia. En el subgrupo con recurrencia isquémica cerebral, el ecocardiograma transesofágico permite establecer el diagnóstico definitivo en el 88,2% de los casos; la principal etiología implicada es la ateromatosis avanzada de la aorta torácica

Caveolin interaction governs Kv1.3 lipid raft targeting

The spatial localization of ion channels at the cell surface is crucial for their functional role. Many channels localize in lipid raft microdomains, which are enriched in cholesterol and sphingolipids. Caveolae, specific lipid rafts which concentrate caveolins, harbor signaling molecules and their targets becoming signaling platforms crucial in cell physiology. However, the molecular mechanisms involved in such spatial localization are under debate. Kv1.3 localizes in lipid rafts and participates in the immunological response. We sought to elucidate the mechanisms of Kv1.3 surface targeting, which govern leukocyte physiology. Kv1 channels share a putative caveolin-binding domain located at the intracellular N-terminal of the channel. This motif, lying close to the S1 transmembrane segment, is situated near the T1 tetramerization domain and the determinants involved in the Kvβ subunit association. The highly hydrophobic domain (FQRQVWLLF) interacts with caveolin 1 targeting Kv1.3 to caveolar rafts. However, subtle variations of this cluster, putative ancillary associations and different structural conformations can impair the caveolin recognition, thereby altering channel's spatial localization. Our results identify a caveolin-binding domain in Kv1 channels and highlight the mechanisms that govern the regulation of channel surface localization during cellular processes