Análisis genético-molecular del papel de la vía endocítica en la ruta de transducción de la señal de pH ambiental en "Aspergillus nidulans"

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Universidad Complutense de Madrid
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Regulation of gene expression by ambient pH in filamentous fungi and yeast is mediated by the pal/RIM signaling pathway and the transcription factor PacC/Rim101. The ambient pH signaling pathway is conserved in the fungal kingdom and has been mainly studied in the filamentous fungus Aspergillus nidulans and in the yeast Saccharomyces cerevisiae, although several studies have also been carried out in the yeasts Yarrowia lipolitica and Candida albicans 45. Ambient pH signal transduction involves the products of the pal genes and the transcription factor PacC in A. nidulans, and the corresponding RIM homologs in S. cerevisiae. The pal/RIM signaling pathway is activated in response to external pH increase. In response to this signal, the PacC transcription factor in A. nidulans and Rim101 in S. cerevisiae are activated by proteolytical processing 17,53. Studies carried out in A. nidulans showed that the proteolytical processing of the transcription factor regulates its nucleo-citoplasmic localization 31. The molecular mechanisms involved in the transduction of the ambient pH signal are highly conserved among fungi. The different components of the pal/PacC signaling pathway in A.nidulans have their corresponding homologs in the RIM pathway in S. cerevisiae. The putative ambient pHsensing complex contains a protein with 7 transmembrane domains (7TM), PalH in A. nidulans 20. In S. cerevisiae, two PalH homologs, Rim21 and Dfg16, have been reported, and both are required for pH signaling 57. Besides these 7TM proteins, there is a 3TM protein, which is also involved in pH signal reception: PalI in A. nidulans and its homolog Rim9 in S. cerevisiae 21,39. Other two main components of the signaling pathway, PalA and PalB in A. nidulans and their respective homologs Rim20 and Rim13 in S. cerevisiae, are likely involved in the proteolytical processing of the transcription factor. PalB/Rim13, which is predicted to be, by sequence analysis, a cysteine protease of the calpain family, appears to be responsible for the pH-dependent proteolytic processing of PacC/Rim101 22,28,41, whereas the proteasome would be responsible for a second proteolytical cleavage in PacC 34. PalA/Rim20 contains a Bro1 domain and interacts with the transcription factor PacC/Rim101 40,55. PalA recognizes two YPXL/I motifs in PacC, located at each side of the first proteolytical cleavage site, and the interaction of PalA with PacC is required for this first proteolytic processing step, presumably catalyzed by PalB 40. A second protein with a Bro1 domain, PalC in A. nidulans and its homolog Ygr122w in S. cerevisiae, appears to have a function in the signal transduction from the pH sensor to the complex involved in proteolytic processing of the transcription factor 38. Finally, our previous work in A. nidulans showed that the last component of this pathway, PalF (Rim8 in S. cerevisiae), interacts with the Cterminal cytoplasmic tail of the 7TM protein PalH...
Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Bioquímica y Biología Molecular I, leída el 03-07-2013
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