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03 Medicina Celular y Molecular.pdf 5474KB May - Centro de ...

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<strong>Medicina</strong> <strong>Celular</strong> y <strong>Molecular</strong> | Cellular and <strong>Molecular</strong> Medicine<br />

64<br />

miguel a. Peñalva<br />

Profesor <strong>de</strong> Investigación | penalva@cib.csic.es<br />

PhD, 1982.<br />

Universidad Autónoma <strong>de</strong> Madrid.<br />

Postdoctoral,<br />

Antibióticos SA (Madrid) e Institut <strong>de</strong> Genetique et<br />

Microbiologie, Universidad <strong>de</strong> París, Orsay.<br />

Científico Titular y Jefe <strong>de</strong> grupo, 1987,<br />

Profesor <strong>de</strong> Investigación <strong>de</strong>s<strong>de</strong> 2001.<br />

CIB, CSIC.<br />

Visiting Scientist, 2005-2006.<br />

MRC Laboratory of <strong>Molecular</strong> Biology, Cambridge UK.<br />

Elegido miembro <strong>de</strong> EMBO en 2000.<br />

Genética <strong>Molecular</strong> <strong>de</strong> Aspergillus<br />

A. nidulans es un mo<strong>de</strong>lo genético para el estudio<br />

<strong>de</strong>l crecimiento celular polarizado y el transporte<br />

a larga distancia (http://en.wikipedia.org/wiki/<br />

Mo<strong>de</strong>l_organism). Sus hifas crecen exclusivamente<br />

por extensión apical, formando células tubulares<br />

Publicaciones Seleccionadas<br />

Selected Publications<br />

Abenza JF, Pantazopoulou A, Rodríguez JM, Galindo<br />

A, Peñalva MA [2009] Long-distance movement of<br />

Aspergillus nidulans early endosomes on microtubule<br />

tracks. Traffic 10: 57-75.<br />

Rodríguez-Galán O, Galindo A, Hervás-Aguilar A, Arst<br />

HN, Jr., Peñalva MA [2009] Physiological involvement<br />

in pH signalling of Vps24-mediated recruitment of<br />

Aspergillus PalB cysteine protease to ESCRT-III. J Biol<br />

Chem 284: 4404-4412.<br />

Pantazopoulou A, Peñalva MA [2009] The<br />

organization and dynamics of the Aspergillus<br />

nidulans Golgi during apical extension and mitosis.<br />

Mol Biol Cell 20: 4335-4337.<br />

Hervás-Aguilar A, Galindo A, Peñalva MA [2010]<br />

Receptor-in<strong>de</strong>pen<strong>de</strong>nt Ambient pH signaling by<br />

ubiquitin attachment to fungal arrestin-like PalF. J<br />

Biol Chem 285: 18095-18102.<br />

Abenza JF, Galindo A, Pantazopoulou A, Gil C, <strong>de</strong><br />

Los Ríos V, Peñalva MA [2010] Aspergillus RabB/Rab5<br />

Integrates Acquisition of Degradative I<strong>de</strong>ntity with<br />

the Long Distance Movement of Early Endosomes.<br />

Mol Biol Cell. 21:2756-2769.<br />

Etxebeste O, Markina-Iñarrairaegui A, Garzia A,<br />

Herrero-García E, Ugal<strong>de</strong> U, Espeso EA. [2009] KapI, a<br />

non-essential member of the Pse1p/Imp5 karyopherin<br />

family, controls colonial and asexual <strong>de</strong>velopment in<br />

Aspergillus nidulans. Microbiology. 155:3934-45.<br />

Etxebeste O, Herrero-García E, Araújo-Bazán L,<br />

Rodríguez-Urra AB, Garzia A, Ugal<strong>de</strong> U, Espeso EA.<br />

[2009] The bZIP-type transcription factor FlbB regulates<br />

distinct morphogenetic stages of colony formation in<br />

Aspergillus nidulans. Mol Microbiol. 73:775-89.<br />

Garzia A, Etxebeste O, Herrero-García E, Ugal<strong>de</strong> U,<br />

Espeso EA. [2010] The concerted action of bZip and<br />

cMyb transcription factors FlbB and FlbD induces<br />

brlA expression and asexual <strong>de</strong>velopment in<br />

Aspergillus nidulans. Mol Microbiol. 75:1314-24.<br />

Etxebeste O, Garzia A, Espeso EA, Ugal<strong>de</strong> U. [2010]<br />

Aspergillus nidulans asexual <strong>de</strong>velopment: making the<br />

most of cellular modules. Trends Microbiol. 18:569-76.<br />

Etxebeste O, Ugal<strong>de</strong> U, Espeso EA. [2010] Adaptative<br />

and <strong>de</strong>velopmental responses to stress in Aspergillus<br />

nidulans. Curr Protein Pept Sci. 11:704-18.<br />

eduardo a. espeso<br />

Científico Titular | eespeso@cib.csic.es<br />

Un aspecto clave <strong>de</strong> los hongos<br />

es su invasividad, asociada con<br />

su rápido crecimiento apical.<br />

Combinando abordajes genéticos con<br />

microscopía multidimensional, estudiamos<br />

la organización <strong>de</strong> Golgi y endosomas<br />

en el contexto <strong>de</strong>l tráfico intracelular<br />

polarizado, centrándonos en GTPasas<br />

Rab y sus efectores. El Golgi <strong>de</strong> Aspergillus<br />

está formado por cisternas dispersas<br />

(Golgi equivalents) que pue<strong>de</strong>n resolverse<br />

por microscopía óptica. Los endosomas<br />

tempranos son característicamente mótiles<br />

a gran<strong>de</strong>s distancias sobre microtúbulos.<br />

La internalización endocítica y la<br />

maduración endosomal son esenciales.<br />

Preten<strong>de</strong>mos compren<strong>de</strong>r los mecanismos<br />

<strong>de</strong> maduración <strong>de</strong> cisternas <strong>de</strong>l Golgi, las<br />

rutas entre éste y los endosomas y el papel<br />

no canónico que los complejos ESCRT<br />

tienen en la organización <strong>de</strong> complejos<br />

<strong>de</strong> transducción <strong>de</strong> señal <strong>de</strong> pH en la<br />

membrana plasmática.<br />

Early and late<br />

cisternae of the nonstacked<br />

Golgi os<br />

Aspergillus. nidulans<br />

can be resolved by<br />

in vivo fluorescence<br />

microscopy, allowing<br />

investigation of<br />

cisternal maturation.<br />

Pantazopoulou<br />

& Peñalva,<br />

“Characterization of<br />

Arpergillus nidulans<br />

RabC/Rab6’ Traffic<br />

12:386 (2011).<br />

PhD, 1989.<br />

Universidad Complutense <strong>de</strong> Madrid.<br />

Postdoctoral, 1997-1999,<br />

EMBO-Postdoctoral Fellow.<br />

Imperial College London.<br />

Contratado Ramón y Cajal, 2001-2004,<br />

Científico Titular y Jefe <strong>de</strong> grupo, 2004.<br />

CIB, CSIC.<br />

Secretario, 2004-2008.<br />

Grupo Especializado <strong>de</strong> Hongos Filamentosos y<br />

Levaduras (SEM).<br />

multinucleadas en las que el tráfico intracelular está<br />

adaptado a las gran<strong>de</strong>s distancias existentes entre<br />

distintas regiones o núcleos <strong>de</strong> la célula. La regulación<br />

<strong>de</strong> la transcripción por pH ambiental media la<br />

adaptación <strong>de</strong> los hongos a ambientes con distinto pH.<br />

Una gran variabilidad genética permite<br />

a los hongos la capacidad <strong>de</strong> medrar en<br />

ambientes extremos. La eficiente regulación<br />

transcripcional y la perfecta comunicación<br />

entre el núcleo y el citoplasma, don<strong>de</strong> se<br />

sintetizan los factores transcripcionales<br />

y concurren muchos <strong>de</strong> los sistemas <strong>de</strong><br />

señalización, aseguran la correcta expresión<br />

<strong>de</strong> aquellos genes cuyos productos se<br />

necesitan para que el hongo se <strong>de</strong>sarrolle<br />

en estas condiciones ambientales.<br />

Estudiamos la maquinaria molecular que<br />

participa en la homeostasis <strong>de</strong> cationes,<br />

mono y divalentes, y la que asegura el<br />

transporte núcleo-citoplásmico <strong>de</strong> factores<br />

transcripcionales <strong>de</strong> alta jerarquía que<br />

permiten afrontar los diferentes estreses<br />

abióticos. Así mismo, preten<strong>de</strong>mos<br />

establecer la forma en la que estos procesos<br />

participan en la diferenciación celular que<br />

ocurre durante el ciclo <strong>de</strong> reproducción<br />

asexual en Aspergillus y en la patogenicidad<br />

<strong>de</strong> este hongo en mamíferos.<br />

Las cisternas tempranas y tardías <strong>de</strong>l Golgi no apilado <strong>de</strong> Aspergillus nidulans pue<strong>de</strong>n<br />

resolverse por microscopía <strong>de</strong> fluorescencia in vivo, lo que permite investigar la<br />

maduración <strong>de</strong> cisternas.<br />

Otros miembros | Other lab members:<br />

Dr. Areti Pantazopoulou Dr. Antonio Galindo Revilla<br />

Dr. Mario Pinar Sala Elena Reoyo<br />

Juan Francisco Abenza Martínez Laura Cobeño Fariñas<br />

Ane Marquina Iñarrairaegui Erika Herrero García<br />

Laura Mellado Maroñas<br />

Patricia Hernán<strong>de</strong>z Ortiz<br />

Daniel Lucena Agell.<br />

www.cib.csic.es/es/grupo.php?idgrupo=8<br />

Fotografías que<br />

muestran la carioferina<br />

kapH-GFP (en ver<strong>de</strong>)<br />

asociada al uso mitótico<br />

durante mitosis cerrada. La<br />

proteina Nud1-mCherry (en<br />

magenta) marca la posición <strong>de</strong>l<br />

“spindle-pole-body” (centrosoma<br />

fúngico). Parte inferior izquierda una<br />

placa maestra con diferentes cepas<br />

y mutantes en el color <strong>de</strong> esporas en<br />

Aspergillus. <strong>Centro</strong> y <strong>de</strong>recha, imágenes<br />

<strong>de</strong> las portadas en Microbiology y Trends in<br />

Microbiology que ilustran el ejemplar don<strong>de</strong> se<br />

han publicado parte <strong>de</strong>l trabajo realizado en el<br />

bienio 09-10.<br />

Insets showing the association of GFP tagged<br />

kariopherin KapH (in green) with the mitotic spindle<br />

during the closed mitosis. Protein Nud1-mCherry (in magenta) labels the position of the spindle pole body, the fungal centrosome. Lower left panel shows different<br />

Aspergillus strains carrying mutations affecting the colour of conidiospores. Centre and right, cover pages of Microbiology and Trends in Microbiology issues, respectively,<br />

where part of our work has been published during years 2009 and 2010.<br />

Aspergillus <strong>Molecular</strong> Genetics<br />

A. nidulans is a genetic mo<strong>de</strong>l for studying polarised<br />

cell growth and long distance transport (http://<br />

en.wikipedia.org/wiki/Mo<strong>de</strong>l_organism). Hyphal tip<br />

cells grow exclusively by apical extension, leading<br />

to tubular multinucleated cells where intracellular<br />

traffic is tailored to the needs imposed by the<br />

relatively large distances between apical and distal<br />

regions and between the different nuclei of the<br />

cell. Regulation of gene expression by ambient pH<br />

mediates fungal adaptation to environments with<br />

different values of pH.<br />

A<br />

key aspect of fungi is their invasiveness, associated with<br />

rapid apical extension. By combining genetic approaches<br />

with multidimensional microscopy, we are studying the<br />

organization of the Golgi and endosomal systems in the context<br />

of polarized traffic, focusing on membrane domain-organising<br />

Rab GTPases and their effectors. The Aspergillus Golgi is formed<br />

by scattered ‘Golgi equivalents’, such that early and late cisternae<br />

can be resolved by optical microscopy. Early endosomes are<br />

characteristically motile for long distances, riding on microtubules.<br />

Endocytic internalization and the maturation of EEs are essential.<br />

We are trying to un<strong>de</strong>rstand the mechanisms of cisternal<br />

maturation in the Golgi, the pathways connecting Golgi and<br />

endosomes and the ‘non-endosomal’ role that ESCRT complexes<br />

play in scaffolding ambient pH signal transduction complexes at<br />

the plasma membrane.<br />

The genetic versatility of fungi allows growth of these organisms in<br />

extreme environments. An efficient transcriptional regulation and<br />

a correct communication between nucleus and cytoplasm, where<br />

transcription factors are synthesised and most of signalling pathways<br />

play their roles, ensure the proper expression of those genes<br />

whose products are nee<strong>de</strong>d by the fungus to <strong>de</strong>velop un<strong>de</strong>r such<br />

extreme ambient conditions. We study the molecular machineries<br />

participating in the homeostasis of mono and divalent cations, and<br />

in nucleo-cytoplasmic trafficking of high hierarchy transcription<br />

factors which allow the fungus to confront diverse abiotic stresses. In<br />

addition, we attempt to establish how these processes contribute to<br />

the cellular differentiation during the asexual reproductive cycle of<br />

Aspergillus and to its pathogenicity in mammals.<br />

65

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