Genetics, Vol 145, 63-73, Copyright © 1997

INVESTIGATIONS

Proteolytic Activation of Rim1p, a Positive Regulator of Yeast Sporulation and Invasive Growth

W. Li and A. P. Mitchell
Department of Microbiology and Institute of Cancer Research, Columbia University, New York, New York 10032

In the yeast Saccharomyces cerevisiae, rim1, 8, 9, or 13 mutations cause four phenotypes: poor growth at low temperature, altered colony morphology, inefficient sporulation due to reduced expression of the meiotic activator IME1, and, as shown here, defective invasive growth. In this report, we have determined the relationship between RIM1 and the other genes, RIM8, 9, and 13, in this group. We have analyzed production of epitope-tagged Rim1p derivatives with HA epitopes at the N-terminus or in the middle of the protein. These Rim1p derivatives exist primarily as a small form (90 kD for Rim1-HA2p) in wild-type cells and as a large form (98 kD for Rim1-HA2p) in rim8, 9, and 13 mutants. We have also analyzed production of {beta}-galactosidase in strains that express a RIM1-lacZ fusion gene. {beta}-galactosidase exists primarily as a ~130 kD form in wild-type cells and as a ~190 kD form in rim9 mutants. These results indicate that Rim1p undergoes C-terminal proteolytic cleavage, and that rim8, 9, and 13 mutations block cleavage. Expression of a Rim1p C-terminal deletion derivative suppresses rim8, 9, and 13 mutations. Thus the phenotypes of rim8, 9, and 13 mutants arise from the defect in Rim1p C-terminal cleavage. Cleavage of Rim1p, like that of its Aspergillus nidulans homologue PacC, is stimulated under alkaline growth conditions. Therefore, Rim1p, PacC and their respective processing pathways may represent a conserved signal transduction pathway.

This article has been cited by other articles:

				S. Blanchin-Roland, G. Da Costa, and C. Gaillardin Ambient pH signalling in the yeast Yarrowia lipolytica involves YlRim23p/PalC, which interacts with Snf7p/Vps32p, but does not require the long C terminus of YlRim9p/PalI Microbiology, June 1, 2008; 154(6): 1668 - 1676. [Abstract] [Full Text] [PDF]

				M. Ikeda, A. Kihara, A. Denpoh, and Y. Igarashi The Rim101 Pathway Is Involved in Rsb1 Expression Induced by Altered Lipid Asymmetry Mol. Biol. Cell, May 1, 2008; 19(5): 1922 - 1931. [Abstract] [Full Text] [PDF]

				A. M. Calcagno-Pizarelli, S. Negrete-Urtasun, S. H. Denison, J. D. Rudnicka, H.-J. Bussink, T. Munera-Huertas, L. Stanton, A. Hervas-Aguilar, E. A. Espeso, J. Tilburn, et al. Establishment of the Ambient pH Signaling Complex in Aspergillus nidulans: PalI Assists Plasma Membrane Localization of PalH Eukaryot. Cell, December 1, 2007; 6(12): 2365 - 2375. [Abstract] [Full Text] [PDF]

				A. Hervas-Aguilar, J. M. Rodriguez, J. Tilburn, H. N. Arst Jr., and M. A. Penalva Evidence for the Direct Involvement of the Proteasome in the Proteolytic Processing of the Aspergillus nidulans Zinc Finger Transcription Factor PacC J. Biol. Chem., November 30, 2007; 282(48): 34735 - 34747. [Abstract] [Full Text] [PDF]

				S. Biswas, P. Van Dijck, and A. Datta Environmental Sensing and Signal Transduction Pathways Regulating Morphopathogenic Determinants of Candida albicans Microbiol. Mol. Biol. Rev., June 1, 2007; 71(2): 348 - 376. [Abstract] [Full Text] [PDF]

				M. M. Penas, A. Hervas-Aguilar, T. Munera-Huertas, E. Reoyo, M. A. Penalva, H. N. Arst Jr., and J. Tilburn Further Characterization of the Signaling Proteolysis Step in the Aspergillus nidulans pH Signal Transduction Pathway Eukaryot. Cell, June 1, 2007; 6(6): 960 - 970. [Abstract] [Full Text] [PDF]

				F. Castrejon, A. Gomez, M. Sanz, A. Duran, and C. Roncero The RIM101 Pathway Contributes to Yeast Cell Wall Assembly and Its Function Becomes Essential in the Absence of Mitogen-Activated Protein Kinase Slt2p Eukaryot. Cell, March 1, 2006; 5(3): 507 - 517. [Abstract] [Full Text] [PDF]

				J. H. Boysen and A. P. Mitchell Control of Bro1-Domain Protein Rim20 Localization by External pH, ESCRT Machinery, and the Saccharomyces cerevisiae Rim101 Pathway Mol. Biol. Cell, March 1, 2006; 17(3): 1344 - 1353. [Abstract] [Full Text] [PDF]

				M. Hayashi, T. Fukuzawa, H. Sorimachi, and T. Maeda Constitutive Activation of the pH-Responsive Rim101 Pathway in Yeast Mutants Defective in Late Steps of the MVB/ESCRT Pathway Mol. Cell. Biol., November 1, 2005; 25(21): 9478 - 9490. [Abstract] [Full Text] [PDF]

				J. Tilburn, J. C. Sanchez-Ferrero, E. Reoyo, H. N. Arst Jr., and M. A. Penalva Mutational Analysis of the pH Signal Transduction Component PalC of Aspergillus nidulans Supports Distant Similarity to BRO1 Domain Family Members Genetics, September 1, 2005; 171(1): 393 - 401. [Abstract] [Full Text] [PDF]

				K. Rothfels, J. C. Tanny, E. Molnar, H. Friesen, C. Commisso, and J. Segall Components of the ESCRT Pathway, DFG16, and YGR122w Are Required for Rim101 To Act as a Corepressor with Nrg1 at the Negative Regulatory Element of the DIT1 Gene of Saccharomyces cerevisiae Mol. Cell. Biol., August 1, 2005; 25(15): 6772 - 6788. [Abstract] [Full Text] [PDF]

				E. T. Arechiga-Carvajal and J. Ruiz-Herrera The RIM101/pacC Homologue from the Basidiomycete Ustilago maydis Is Functional in Multiple pH-Sensitive Phenomena Eukaryot. Cell, June 1, 2005; 4(6): 999 - 1008. [Abstract] [Full Text] [PDF]

				K. J. Barwell, J. H. Boysen, W. Xu, and A. P. Mitchell Relationship of DFG16 to the Rim101p pH Response Pathway in Saccharomyces cerevisiae and Candida albicans Eukaryot. Cell, May 1, 2005; 4(5): 890 - 899. [Abstract] [Full Text] [PDF]

				A. L. Kullas, M. Li, and D. A. Davis Snf7p, a Component of the ESCRT-III Protein Complex, Is an Upstream Member of the RIM101 Pathway in Candida albicans Eukaryot. Cell, December 1, 2004; 3(6): 1609 - 1618. [Abstract] [Full Text] [PDF]

				W. Xu, F. J. Smith Jr., R. Subaran, and A. P. Mitchell Multivesicular Body-ESCRT Components Function in pH Response Regulation in Saccharomyces cerevisiae and Candida albicans Mol. Biol. Cell, December 1, 2004; 15(12): 5528 - 5537. [Abstract] [Full Text] [PDF]

				M. Li, S. J. Martin, V. M. Bruno, A. P. Mitchell, and D. A. Davis Candida albicans Rim13p, a Protease Required for Rim101p Processing at Acidic and Alkaline pHs Eukaryot. Cell, June 1, 2004; 3(3): 741 - 751. [Abstract] [Full Text] [PDF]

				H. Lotz, K. Sohn, H. Brunner, F. A. Muhlschlegel, and S. Rupp RBR1, a Novel pH-Regulated Cell Wall Gene of Candida albicans, Is Repressed by RIM101 and Activated by NRG1 Eukaryot. Cell, June 1, 2004; 3(3): 776 - 784. [Abstract] [Full Text] [PDF]

				M. Eisendle, H. Oberegger, R. Buttinger, P. Illmer, and H. Haas Biosynthesis and Uptake of Siderophores Is Controlled by the PacC-Mediated Ambient-pH Regulatory System in Aspergillus nidulans Eukaryot. Cell, April 1, 2004; 3(2): 561 - 563. [Abstract] [Full Text] [PDF]

				E. Spreghini, D. A. Davis, R. Subaran, M. Kim, and A. P. Mitchell Roles of Candida albicans Dfg5p and Dcw1p Cell Surface Proteins in Growth and Hypha Formation Eukaryot. Cell, August 1, 2003; 2(4): 746 - 755. [Abstract] [Full Text] [PDF]

				O. Vincent, L. Rainbow, J. Tilburn, H. N. Arst Jr., and M. A. Penalva YPXL/I Is a Protein Interaction Motif Recognized by Aspergillus PalA and Its Human Homologue, AIP1/Alix Mol. Cell. Biol., March 1, 2003; 23(5): 1647 - 1655. [Abstract] [Full Text] [PDF]

				T. M. Lamb and A. P. Mitchell The Transcription Factor Rim101p Governs Ion Tolerance and Cell Differentiation by Direct Repression of the Regulatory Genes NRG1 and SMP1 in Saccharomyces cerevisiae Mol. Cell. Biol., January 15, 2003; 23(2): 677 - 686. [Abstract] [Full Text] [PDF]

				A. H. Enyenihi and W. S. Saunders Large-Scale Functional Genomic Analysis of Sporulation and Meiosis in Saccharomyces cerevisiae Genetics, January 1, 2003; 163(1): 47 - 54. [Abstract] [Full Text] [PDF]

				D. A. Davis, V. M. Bruno, L. Loza, S. G. Filler, and A. P. Mitchell Candida albicans Mds3p, a Conserved Regulator of pH Responses and Virulence Identified Through Insertional Mutagenesis Genetics, December 1, 2002; 162(4): 1573 - 1581. [Abstract] [Full Text] [PDF]

				M. A. Penalva and H. N. Arst Jr. Regulation of Gene Expression by Ambient pH in Filamentous Fungi and Yeasts Microbiol. Mol. Biol. Rev., September 1, 2002; 66(3): 426 - 446. [Abstract] [Full Text] [PDF]

				S. P. Palecek, A. S. Parikh, and S. J. Kron Sensing, signalling and integrating physical processes during Saccharomyces cerevisiae invasive and filamentous growth Microbiology, April 1, 2002; 148(4): 893 - 907. [Full Text] [PDF]

				C. I. Gonzalez-Lopez, R. Szabo, S. Blanchin-Roland, and C. Gaillardin Genetic Control of Extracellular Protease Synthesis in the Yeast Yarrowia lipolytica Genetics, February 1, 2002; 160(2): 417 - 427. [Abstract] [Full Text] [PDF]

				W. Xu and A. P. Mitchell Yeast PalA/AIP1/Alix Homolog Rim20p Associates with a PEST-Like Region and Is Required for Its Proteolytic Cleavage J. Bacteriol., December 1, 2001; 183(23): 6917 - 6923. [Abstract] [Full Text] [PDF]

				M. Richard, R. R. Quijano, S. Bezzate, F. Bordon-Pallier, and C. Gaillardin Tagging Morphogenetic Genes by Insertional Mutagenesis in the Yeast Yarrowia lipolytica J. Bacteriol., May 15, 2001; 183(10): 3098 - 3107. [Abstract] [Full Text]

				J. M. Mingot, E. A. Espeso, E. Díez, and M. A. Peñalva Ambient pH Signaling Regulates Nuclear Localization of the Aspergillus nidulans PacC Transcription Factor Mol. Cell. Biol., March 1, 2001; 21(5): 1688 - 1699. [Abstract] [Full Text]

				D. Cavalieri, J. P. Townsend, and D. L. Hartl Manifold anomalies in gene expression in a vineyard isolate of Saccharomyces cerevisiae revealed by DNA microarray analysis PNAS, October 12, 2000; (2000) 210395297. [Abstract] [Full Text]

				D. Davis, J. E. Edwards Jr., A. P. Mitchell, and A. S. Ibrahim Candida albicans RIM101 pH Response Pathway Is Required for Host-Pathogen Interactions Infect. Immun., October 1, 2000; 68(10): 5953 - 5959. [Abstract] [Full Text] [PDF]

				A. El Barkani, O. Kurzai, W. A. Fonzi, A. Ramon, A. Porta, M. Frosch, and F. A. Mühlschlegel Dominant Active Alleles of RIM101 (PRR2) Bypass the pH Restriction on Filamentation of Candida albicans Mol. Cell. Biol., July 1, 2000; 20(13): 4635 - 4647. [Abstract] [Full Text]

				D. Davis, R. B. Wilson, and A. P. Mitchell RIM101-Dependent and -Independent Pathways Govern pH Responses in Candida albicans Mol. Cell. Biol., February 1, 2000; 20(3): 971 - 978. [Abstract] [Full Text]

				A. Porta, A. M. Ramon, and W. A. Fonzi PRR1, a Homolog of Aspergillus nidulans palF, Controls pH-Dependent Gene Expression and Filamentation in Candida albicans J. Bacteriol., December 15, 1999; 181(24): 7516 - 7523. [Abstract] [Full Text]

				A. M. Ramon, A. Porta, and W. A. Fonzi Effect of Environmental pH on Morphological Development of Candida albicans Is Mediated via the PacC-Related Transcription Factor Encoded by PRR2 J. Bacteriol., December 15, 1999; 181(24): 7524 - 7530. [Abstract] [Full Text]

				R. B. Wilson, D. Davis, and A. P. Mitchell Rapid Hypothesis Testing with Candida albicans through Gene Disruption with Short Homology Regions J. Bacteriol., March 15, 1999; 181(6): 1868 - 1874. [Abstract] [Full Text]

				J.-M. Mingot, J. Tilburn, E. Diez, E. Bignell, M. Orejas, D. A. Widdick, S. Sarkar, C. V. Brown, M. X. Caddick, E. A. Espeso, et al. Specificity Determinants of Proteolytic Processing of Aspergillus PacC Transcription Factor Are Remote from the Processing Site, and Processing Occurs in Yeast If pH Signalling Is Bypassed Mol. Cell. Biol., February 1, 1999; 19(2): 1390 - 1400. [Abstract] [Full Text] [PDF]

				S. M. Honigberg and R. H. Lee Snf1 Kinase Connects Nutritional Pathways Controlling Meiosis in Saccharomyces cerevisiae Mol. Cell. Biol., August 1, 1998; 18(8): 4548 - 4555. [Abstract] [Full Text]

				S. Sagee, A. Sherman, G. Shenhar, K. Robzyk, N. Ben-Doy, G. Simchen, and Y. Kassir Multiple and Distinct Activation and Repression Sequences Mediate the Regulated Transcription of IME1, a Transcriptional Activator of Meiosis-Specific Genes in Saccharomyces cerevisiae Mol. Cell. Biol., April 1, 1998; 18(4): 1985 - 1995. [Abstract] [Full Text]

				S. A. Phillips, V. A. Barr, D. H. Haft, S. I. Taylor, and C. R. Haft Identification and Characterization of SNX15, a Novel Sorting Nexin Involved in Protein Trafficking J. Biol. Chem., February 9, 2001; 276(7): 5074 - 5084. [Abstract] [Full Text] [PDF]

				T. M. Lamb, W. Xu, A. Diamond, and A. P. Mitchell Alkaline Response Genes of Saccharomyces cerevisiae and Their Relationship to the RIM101 Pathway J. Biol. Chem., January 12, 2001; 276(3): 1850 - 1856. [Abstract] [Full Text] [PDF]

				D. Cavalieri, J. P. Townsend, and D. L. Hartl Manifold anomalies in gene expression in a vineyard isolate of Saccharomyces cerevisiae revealed by DNA microarray analysis PNAS, October 24, 2000; 97(22): 12369 - 12374. [Abstract] [Full Text] [PDF]