Wednesday, 12th December 2018
Cell Biology and Immunology
  Tetraspanin-enriched membrane microdomains in extracellular vesicles and cell adhesion and migration

 


Grupo-400

 


 

 

María Yáñez-Mó

 ASciStaff

APublications

 

 

 

 

Research summary:

Our group is focused on the characterization of tetraspanin-enriched microdomains (TEMs), specialized membrane platforms involved in cell-cell adhesion and migration processes as reviewed in 2009 in Trends in Cell Biology (2009).

figura1

Figure 1: Tetraspanin-enriched microdomains and their functions. It has been demonstrated that TEM-induced clustering or segregation of adhesion receptors and signalling molecules plays a functional role in phenomena related to migration and invasion, intercellular adhesion, membrane fusion events and intracellular trafficking. These phenomena are implicated in several biological processes. From Yáñez-Mó et al., Trends Cell Biol. 2009 Sep;19(9):434-46

We have developed two main lines of research. The first one is devoted to the study of membrane-bound proteases, and how their activity is regulated by their inclusion into TEMs, such as in the case of MT1-MMP/CD151/alpha3beta1 integrin ternary complexes.

A second line of research is devoted to the characterization of tetraspanins intracellular connections. Starting with a high throughput proteomic screen, we thereafter study the relevance of the molecular interactions found, in cellular models for fundamental processes of the biology of the immune system (leukocyte migration, immune synapse formation) or tumor cell motility.

figura2

Figure 2: Protein interaction networks for CD81 and EWI-2 ligands identified in human primary lymphoblast-derived exosomes. A, intracellular ligands of CD81 and EWI-2 were manually clustered into groups according to their function using the IPA analysis program. Symbol size is proportional to the number of peptides identified for each protein in the pull-down assays. B, proportions of proteins in exosomes that were identified as ligands of EWI-2 and CD81 in exosomes. The proportions were calculated on the basis of the number of peptides identified per protein in total exosome lysates. From Perez-Hernandez D, Gutiérrez-Vázquez C, Jorge I, López-Martín S, Ursa A, Sánchez-Madrid F, Vázquez J, Yáñez-Mó M. J Biol Chem. 2013 Apr 26;288(17):11649-61

figura3

Figure 3: Tetraspanins in extracelular vesicle formation and function. Tetraspanins have the capacity to interact with several receptor and signaling molecules at the membrane, organizing specialized tetraspanin-enriched microdomains (TEMs) that may play a role in (A) EV biogenesis, (B) the selection of exosome cargo (proteins and miRNAs), (C) the binding and uptake of exosomes by target cells, or (D) the ability of exosomes to present antigen in the context of an immune response. From Andreu Z and Yáñez-Mó M. Front Immunol. 2014 Sep 16;5:442. doi: 10.3389/fimmu.2014.00442

 

Intracellular connections of tetraspanin-enriched microdomains led us also to the field of extracellular vesicle (EV) research, since tetraspanin proteins are among the most abundant proteins on EV. Extracellular vesicles, including microvesicles, ectosomes, shedding vesicles, microparticles and exosomes, represent a novel mechanism of intercellular communication as vehicles for intercellular transfer of functional membrane and cytosolic proteins, lipids, and RNAs.


 

Relevant publications:

  • Biological properties of extracellular vesicles and their physiological functions. Yáñez-Mó M, Siljander PR, Andreu Z, Zavec AB, Borràs FE, Buzas EI, Buzas K, Casal E, Cappello F, Carvalho J, Colás E, Cordeiro-da Silva A, Fais S, Falcon-Perez JM, Ghobrial IM, Giebel B, Gimona M, Graner M, Gursel I, Gursel M, Heegaard NH, Hendrix A, Kierulf P, Kokubun K, Kosanovic M, Kralj-Iglic V, Krämer-Albers EM, Laitinen S, Lässer C, Lener T, Ligeti E, Linē A, Lipps G, Llorente A, Lötvall J, Manček-Keber M, Marcilla A, Mittelbrunn M, Nazarenko I, Nolte-'t Hoen EN, Nyman TA, O'Driscoll L, Olivan M, Oliveira C, Pállinger É, Del Portillo HA, Reventós J, Rigau M, Rohde E, Sammar M, Sánchez-Madrid F, Santarém N, Schallmoser K, Ostenfeld MS, Stoorvogel W, Stukelj R, Van der Grein SG, Vasconcelos MH, Wauben MH, De Wever O.J Extracell Vesicles. 2015 May 14;4:27066. doi: 10.3402/jev.v4.27066. eCollection 2015. PMID: 25979354
  • Tetraspanins in extracellular vesicle formation and function. Andreu Z, Yáñez-Mó M. Front Immunol. 2014 Sep 16;5:442. doi: 10.3389/fimmu.2014.00442. eCollection 2014. Review. PMID: 25278937
  • The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. Perez-Hernandez D, Gutiérrez-Vázquez C, Jorge I, López-Martín S, Ursa A, Sánchez-Madrid F, Vázquez J, Yáñez-Mó M. J Biol Chem. 2013 Apr 26;288(17):11649-61. doi:10.1074/jbc.M112.445304. Epub 2013 Mar 5. PMID: 23463506
  • CD81 regulates cell migration through its association with Rac GTPase. Tejera E, Rocha-Perugini V, López-Martín S, Pérez-Hernández D, Bachir AI, Horwitz AR, Vázquez J, Sánchez-Madrid F, Yáñez-Mo M. Mol Biol Cell. 2013 Feb;24(3):261-73. doi: 10.1091/mbc.E12-09-0642. Epub 2012 Dec 21. PMID: 23264468
  • EWI-2 association with α-actinin regulates T cell immune synapses and HIV viral infection. Gordón-Alonso M, Sala-Valdés M, Rocha-Perugini V, Pérez-Hernández D, López-Martín S, Ursa A, Alvarez S, Kolesnikova TV, Vázquez J, Sánchez-Madrid F, Yáñez-Mó M. J Immunol. 2012 Jul 15;189(2):689-700

NOTE! This site uses cookies and similar technologies.

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

I understand

COOKIES POLICY

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:

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: