Metabolic homeostasis

Research summary:

The transition metal copper (Cu+) is an essential trace element for all biota. Its redox properties bestow Cu with capabilities that are simultaneously essential and potentially damaging to the cell. Free Cu is virtually absent in the cell. In mammalians liver is the major captor, distributor and excreter of Cu. Humans eliminate 95% of the Cu+ ingested with diet. The excretion of Cu into the bile is an attribute exclusive of the hepatocyte and bile is the major route of Cu elimination and the most important mechanism in Cu homoeostasis in mammals. The correlation between the release of ATP7B retained in the trans-Golgi network (TGN) and the role of ATP7B in excretion of Cu into the bile is firmly established. Yet, the pathway of ATP7B transport is poorly understood and its site of action is the subject of a hot debate. Our studies of Cu+-mediated ATP7B traffic in CAN 10 hepatoma cells showed that after its release from the TGN, ATP7B is basolateral sorted, inserted in the basolateral plasma membrane and transported by transcytosis to the bile canaliculus (BC). Insertion of ATP7B into the membrane of the BC is essential for excreting excess of cellular Cu+ into the medium. Contradicting recent reports, our studies find no evidence of ATP7B association with lysosomes and do not support the recent model of Cu+ excretion mediated by lysosome exocytosis. In recent months we have started a systematic study of the mutations that disrupt ATP7B traffic and cause Wilson disease and cuprotoxicosis with a genetic background of wild ATP7B. In a separate study we investigate the role of ESyt proteins in membrane dynamics and glucose and lipid metabolism in the adipocyte. New inroads in understanding the functioning of Esyt3, a protein associated with the endoplasmic reticulum (ER) that is believed to play a key role in anchoring the ER to the plasma membrane, include: the mapping of the Ca++ and phospholipid binding to the BM y C2-1,C2-2 y C2-3 domains; the characterization of its physical interaction with gelsolin; its role in lipid droplet biogenesis.

Finally the study of the toroidal structure produced by polymerization of IMPDH2 is in progress and the study of the HDAC enhancer C6orf89 has been completed.

Cu+- induced relocation of the Cutransporter ATP7B from the trans-Golgi network to the bile canaliculus in CAN 10 hepatoma cells. Cells treated with Cu+ as indicated in the panels were studied for ATP7B location. Note the early transit of ATP7B through the cell basolateral domain (area delineated by the white dotted lines and the far end of the β catenin labelled plasma membrane) and the localization of ATP7B in the bile canaliculi, sealed by the ZO-1 positive tight junctions, after extensive treatment with Cu+.


* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
Pulido VegaDiego4074436dpulido(at)cbm.csic.esE.Científicos Titulares de Organismos Públicos de Investigación

Relevant publications:

  • DKWSLLL, a versatile DXXXLL-type signal with distinct roles in the Cu(+)-regulated trafficking of ATP7B.Lalioti V, Hernandez-Tiedra S, Sandoval IV.Traffic. 2014 Aug;15(8):839-60. 2014 Jun 24.
  • Sorcin links calcium signaling to vesicle trafficking, regulates Polo-like kinase 1 and is necessary for mitosis. Lalioti VS, Ilari A, O'Connell DJ, Poser E, Sandoval IV, Colotti G.PLoS One. 2014 Jan 10;
  • Molecular mechanism and functional role of brefeldin A-mediated ADP-ribosylation of CtBP1/BARS. Colanzi A, Grimaldi G, Catara G, Valente C, Cericola C, Liberali P, Ronci M, Lalioti VS, Bruno A, Beccari AR, Urbani A, De Flora A, Nardini M, Bolognesi M, Luini A, Corda D. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9794-9. doi: 10.1073/pnas.1222413110. Epub 2013 May 28.
  • C6orf89 encodes three distinct HDAC enhancers that function in the nucleolus, the golgi and the midbody. Lalioti VS, Vergarajauregui S, Villasante A, Pulido D, Sandoval IV.J Cell Physiol. 2013 Sep;228(9):1907-21.

NOTE! This site uses cookies and similar technologies.

If you not change browser settings, you agree to it. Learn more

I understand


What are cookies?

A cookie is a file that is downloaded to your computer when you access certain web pages. Cookies allow a web page, among other things, to store and retrieve information about the browsing habits of a user or their equipment and, depending on the information they contain and the way they use their equipment, they can be used to recognize the user.

Types of cookies

Classification of cookies is made according to a series of categories. However, it is necessary to take into account that the same cookie can be included in more than one category.

  1. Cookies according to the entity that manages them

    Depending on the entity that manages the computer or domain from which the cookies are sent and treat the data obtained, we can distinguish:

    • Own cookies: those that are sent to the user's terminal equipment from a computer or domain managed by the editor itself and from which the service requested by the user is provided.
    • Third party cookies: those that are sent to the user's terminal equipment from a computer or domain that is not managed by the publisher, but by another entity that processes the data obtained through the cookies. When cookies are installed from a computer or domain managed by the publisher itself, but the information collected through them is managed by a third party, they cannot be considered as own cookies.

  2. Cookies according to the period of time they remain activated

    Depending on the length of time that they remain activated in the terminal equipment, we can distinguish:

    • Session cookies: type of cookies designed to collect and store data while the user accesses a web page. They are usually used to store information that only is kept to provide the service requested by the user on a single occasion (e.g. a list of products purchased).
    • Persistent cookies: type of cookies in which the data is still stored in the terminal and can be accessed and processed during a period defined by the person responsible for the cookie, which can range from a few minutes to several years.

  3. Cookies according to their purpose

    Depending on the purpose for which the data obtained through cookies are processed, we can distinguish between:

    • Technical cookies: those that allow the user to navigate through a web page, platform or application and the use of different options or services that exist in it, such as controlling traffic and data communication, identifying the session, access to restricted access parts, remember the elements that make up an order, perform the purchase process of an order, make a registration or participation in an event, use security elements during navigation, store content for the broadcast videos or sound or share content through social networks.
    • Personalization cookies: those that allow the user to access the service with some predefined general characteristics based on a series of criteria in the user's terminal, such as the language, the type of browser through which the user accesses the service, the regional configuration from where you access the service, etc.
    • Analytical cookies: those that allow the person responsible for them to monitor and analyse the behaviour of the users of the websites to which they are linked. The information collected through this type of cookies is used in the measurement of the activity of the websites, applications or platforms, and for the elaboration of navigation profiles of the users of said sites, applications and platforms, in order to introduce improvements in the analysis of the data of use made by the users of the service.

Cookies used on our website

The CBMSO website uses Google Analytics. Google Analytics is a simple and easy to use tool that helps website owners to measure how users interact with the content of the site. You can consult more information about the cookies used by Google Analitycs in this link.

Acceptance of the Cookies Policy

The CBMSO assumes that you accept the use of cookies if you continue browsing, considering that it is a conscious and positive action from which the user's consent is inferred. In this regard, you are previously informed that such behaviour will be interpreted that you accept the installation and use of cookies.

Knowing this information, it is possible to carry out the following actions:

  • Accept cookies: if the user presses the acceptance button, this warning will not be displayed again when accessing any page of the portal.
  • Review the cookies policy: the user can access to this page in which the use of cookies is detailed, as well as links to modify the browser settings.

How to modify the configuration of cookies

Using your browser you can restrict, block or delete cookies from any web page. In each browser the process is different, here we show you links on this particular of the most used browsers: