Zinc signaling

Laboratory of Molecular Physiology

Cell and Molecular Biology Program

Department of Medicine and Life Sciences

Edifici PRBB (campus del Mar)
Doctor Aiguader, 88
08003 Barcelona

 (+34) 93 316 08 54

[email protected]

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Zinc signaling is the research team led by Dr. Rubén Vicente. Zinc is a trace element essential for human health. The World Health Organization estimates that zinc deficiency affects about 30% of the world's population. This condition causes immune dysfunction and neurodevelopmental disorders.  Similarly to calcium, zinc acts as a second messenger participating in different cellular processes. The main interest of the team is to understand how zinc signaling functions within the immune and nervous systems. The current research projects are:

Zinc signaling in immune cells

Zinc deficiency leads to an increased risk of inflammatory and infectious diseases. However, the specific role of zinc in the physiology of T-cells is still poorly characterized. Zinc is known to affect T lymphocyte maturation, differentiation, and cytokine production.  Our laboratory has demonstrated that zinc positively potentiates T-cell function by enhancing the three main signaling activation pathways, AP-1, NF-kB, and NFAT1. In addition, we have described that the Zip6 zinc transporter is essential for proper T-cell activation.  We aim to have a better knowledge of the signaling events that modulate zinc in T to understand the benefits and risks of zinc-based nutritional immunity.

Zinc signaling in the nervous system

Zinc participates actively in the nervous system function. It is concentrated in synaptic vesicles of large populations of glutamatergic neurons such as the cerebral cortex, hippocampus or amygdala. Zinc modulates neurotransmission by lowering glutamatergic excitability. However, excessive zinc can be toxic, leading to neuronal death during events like stroke (ischemia) or seizures. This toxicity is thought to be caused by damage to mitochondria and the production of reactive oxygen species (ROS). Our research aims to understand and control how zinc moves in and out of mitochondria to prevent this neurotoxicity.

Previous projects of the team

- Zip4 as a target for pancreatic cancer therapy (NanoTarg technology)

- ORMDL3 pathophysiology

 

 

 

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Researchers

Silvia Cassinelli

Cassinelli, Silvia
Postdoctoral Researcher
Biophysics of the immune system

Gutiérrez García, Esteban
PhD Student
Biophysics of the immune system

Cristina Plata Fernández

Plata Fernández, Cristina
Technician & Lab manager
Molecular Physiology Lab

Rubén Vicente García

Vicente García, Rubén
Principal Investigator
Biophysics of the immune system

Asset Publisher

Relevant Publications

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  1. Cantero-Recasens G, Fandos C, Rubio-Moscardo F, Valverde MA, Vicente R.(2010) The asthma-associated ORMDL3 gene product regulates endoplasmic reticulum-mediated calcium signaling and cellular stress. Hum Mol Genet. 19, 111-21.
  2. Carreras-Sureda A, Cantero-Recasens G, Rubio-Moscardo F, Kiefer K, Peinelt C, Niemeyer BA, Valverde MA, Vicente R. (2013) ORMDL3 modulates store-operated calcium entry and lymphocyte activation. Hum Mol Genet.  22:519-30.
  3. Engelken J, Carnero-Montoro E, Pybus M, Andrews GK, Lalueza-Fox C, Comas D, Sekler I, de la Rasilla M, Rosas A, Stoneking M, Valverde MA, Vicente R*, Bosch E*. (2014)Extreme population differences in the human zinc transporter ZIP4 (SLC39A4) are explained by positive selection in Sub-Saharan Africa. PLoS Genet. 10(2):e1004128. * both laboratories contributed equally
  4. Kiefer K, Carreras-Sureda A, García-López R, Rubio-Moscardó F, Casas J, Fabriàs G, Vicente R. (2015) Coordinated regulation of the orosomucoid-like gene family expression controls de novo ceramide synthesis in mammalian cells. J Biol Chem. Jan 30;290(5):2822-30. doi: 10.1074/jbc.M114.595116. Epub 2014 Dec 17.
  5. Orta-Mascaró M, Consuegra-Fernández M, Carreras E, Roncagalli R, Carreras-Sureda A, Alvarez P, Girard L, Simões I, Martínez-Florensa M, Aranda F, Merino R, Martínez VG, Vicente R, Merino J, Sarukhan A, Malissen M, Malissen B, Lozano F. (2016) CD6 modulates thymocyte selection and peripheral T cell homeostasis. J Exp Med. Jul 25;213(8):1387-97. doi: 10.1084/jem.20151785. Epub 2016 Jul 4.
  6. Carreras-Sureda A, Rubio-Moscardo F, Olvera A, Argilaguet J, Kiefer K, Mothe B, Meyerhans A, Brander C, Vicente R. Lymphocyte Activation Dynamics Is Shaped by Hereditary Components at Chromosome Region 17q12-q21. PLoS One. 2016 Nov 11;11(11):e0166414. doi: 10.1371/journal.pone.0166414.
  7. Matalonga J, Glaria E, Bresque M, Escande C, Carbó JM, Kiefer K, Vicente R, León TE, Beceiro S, Pascual-García M, Serret J, Sanjurjo L, Morón-Ros S, Riera A, Paytubi S, Juarez A, Sotillo F, Lindbom L, Caelles C, Sarrias MR, Sancho J, Castrillo A, Chini EN, Valledor AF. (2017) The Nuclear Receptor LXR Limits Bacterial Infection of Host Macrophages through a Mechanism that Impacts Cellular NAD Metabolism. Cell Rep. 2017 Jan 31;18(5):1241-1255. doi: 10.1016/j.celrep.2017.01.007.
  8. Colomar N, Meseguer A, Company I, Jutz S, Olvera A, Kiefer K, Brander C, Herrera-Fernández V, Steinberger P and Vicente R. Zip6 transporter is an essential component of the lymphocyte activation machinery. J. Immunol  2019 Jan 15;202(2):441-450. doi: 10.4049/jimmunol.1800689
  9. Kiefer K, Casas J, García-López R, Vicente R. Ceramide Imbalance and Impaired TLR4-Mediated Autophagy in BMDM of an ORMDL3-Overexpressing Mouse Model. Int J Mol Sci. 2019 Mar 20;20(6). doi: 10.3390/ijms20061391.
  10. Carreras-Sureda A, Jaña F, Ramos-Fernández E, Urra H, van Vliet AR, Durand S, Mortenson D, Pihan P, Gonzalez-Quiroz M, Vicente R, Inestrosa N, Wiseman L, Agostinis P, Bultynck G, Court F, Kroemer G, Cárdenas JC and Hetz C. Non-canonical function of the unfolded protein response sensor IRE1α as a structural determinant of mitochondrial-associated ER membranes Nat Cell Biol 2019 Jun;21(6):755-767. doi: 10.1038/s41556-019-0329-y.
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