Protein kinase A regulatory subunit isoforms regulate growth and differentiation in Mucor circinelloides: Essential role of pkaR4
The protein kinase A (PKA) signaling pathway plays a role in regulating growth and differentiation in the dimorphic fungus Mucor circinelloides. PKA holoenzyme is comprised of two catalytic (C) and two regulatory (R) subunits. In M. circinelloides, four genes encode the PKAR1, PKAR2, PKAR3, and PKAR...
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paper:paper_15359778_v11_n8_p989_Ocampo2023-06-08T16:20:07Z Protein kinase A regulatory subunit isoforms regulate growth and differentiation in Mucor circinelloides: Essential role of pkaR4 Ocampo, Josefina Moreno de Colonna, Silvia Rossi, Silvia Graciela cyclic AMP dependent protein kinase fungal protein holoenzyme isoprotein article enzymology fungus spore gene deletion genetics growth, development and aging metabolism morphogenesis Mucor protein subunit signal transduction ubiquitination Cyclic AMP-Dependent Protein Kinases Fungal Proteins Gene Deletion Holoenzymes Morphogenesis Mucor Protein Isoforms Protein Subunits Signal Transduction Spores, Fungal Ubiquitination Fungi Mucor circinelloides The protein kinase A (PKA) signaling pathway plays a role in regulating growth and differentiation in the dimorphic fungus Mucor circinelloides. PKA holoenzyme is comprised of two catalytic (C) and two regulatory (R) subunits. In M. circinelloides, four genes encode the PKAR1, PKAR2, PKAR3, and PKAR4 isoforms of R subunits. We have constructed null mutants and demonstrate that each isoform has a different role in growth and differentiation. The most striking finding is that pkaR4 is an essential gene, because only heterokaryons were obtained in knockout experiments. Heterokaryons with low levels of wild-type nuclei showed an impediment in the emission of the germ tube, suggesting a pivotal role of this gene in germ tube emergence. The remaining null strains showed different alterations in germ tube emergence, sporulation, and volume of the mother cell. The pkaR2 null mutant showed an accelerated germ tube emission and was the only mutant that germinated under anaerobic conditions when glycine was used as a nitrogen source, suggesting that pkaR2 participates in germ tube emergence by repressing it. From the measurement of the mRNA and protein levels of each isoform in the wild-type and knockout strains, it can be concluded that the expression of each subunit has its own mechanism of differential regulation. The PKAR1 and PKAR2 isoforms are posttranslationally modified by ubiquitylation, suggesting another regulation point in the specificity of the signal transduction. The results indicate that each R isoform has a different role in M. circinelloides physiology, controlling the dimorphism and contributing to the specificity of cyclic AMP (cAMP)-PKA pathway. © 2012, American Society for Microbiology. All Rights Reserved. Fil:Ocampo, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Moreno, S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rossi, S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15359778_v11_n8_p989_Ocampo http://hdl.handle.net/20.500.12110/paper_15359778_v11_n8_p989_Ocampo |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
cyclic AMP dependent protein kinase fungal protein holoenzyme isoprotein article enzymology fungus spore gene deletion genetics growth, development and aging metabolism morphogenesis Mucor protein subunit signal transduction ubiquitination Cyclic AMP-Dependent Protein Kinases Fungal Proteins Gene Deletion Holoenzymes Morphogenesis Mucor Protein Isoforms Protein Subunits Signal Transduction Spores, Fungal Ubiquitination Fungi Mucor circinelloides |
spellingShingle |
cyclic AMP dependent protein kinase fungal protein holoenzyme isoprotein article enzymology fungus spore gene deletion genetics growth, development and aging metabolism morphogenesis Mucor protein subunit signal transduction ubiquitination Cyclic AMP-Dependent Protein Kinases Fungal Proteins Gene Deletion Holoenzymes Morphogenesis Mucor Protein Isoforms Protein Subunits Signal Transduction Spores, Fungal Ubiquitination Fungi Mucor circinelloides Ocampo, Josefina Moreno de Colonna, Silvia Rossi, Silvia Graciela Protein kinase A regulatory subunit isoforms regulate growth and differentiation in Mucor circinelloides: Essential role of pkaR4 |
topic_facet |
cyclic AMP dependent protein kinase fungal protein holoenzyme isoprotein article enzymology fungus spore gene deletion genetics growth, development and aging metabolism morphogenesis Mucor protein subunit signal transduction ubiquitination Cyclic AMP-Dependent Protein Kinases Fungal Proteins Gene Deletion Holoenzymes Morphogenesis Mucor Protein Isoforms Protein Subunits Signal Transduction Spores, Fungal Ubiquitination Fungi Mucor circinelloides |
description |
The protein kinase A (PKA) signaling pathway plays a role in regulating growth and differentiation in the dimorphic fungus Mucor circinelloides. PKA holoenzyme is comprised of two catalytic (C) and two regulatory (R) subunits. In M. circinelloides, four genes encode the PKAR1, PKAR2, PKAR3, and PKAR4 isoforms of R subunits. We have constructed null mutants and demonstrate that each isoform has a different role in growth and differentiation. The most striking finding is that pkaR4 is an essential gene, because only heterokaryons were obtained in knockout experiments. Heterokaryons with low levels of wild-type nuclei showed an impediment in the emission of the germ tube, suggesting a pivotal role of this gene in germ tube emergence. The remaining null strains showed different alterations in germ tube emergence, sporulation, and volume of the mother cell. The pkaR2 null mutant showed an accelerated germ tube emission and was the only mutant that germinated under anaerobic conditions when glycine was used as a nitrogen source, suggesting that pkaR2 participates in germ tube emergence by repressing it. From the measurement of the mRNA and protein levels of each isoform in the wild-type and knockout strains, it can be concluded that the expression of each subunit has its own mechanism of differential regulation. The PKAR1 and PKAR2 isoforms are posttranslationally modified by ubiquitylation, suggesting another regulation point in the specificity of the signal transduction. The results indicate that each R isoform has a different role in M. circinelloides physiology, controlling the dimorphism and contributing to the specificity of cyclic AMP (cAMP)-PKA pathway. © 2012, American Society for Microbiology. All Rights Reserved. |
author |
Ocampo, Josefina Moreno de Colonna, Silvia Rossi, Silvia Graciela |
author_facet |
Ocampo, Josefina Moreno de Colonna, Silvia Rossi, Silvia Graciela |
author_sort |
Ocampo, Josefina |
title |
Protein kinase A regulatory subunit isoforms regulate growth and differentiation in Mucor circinelloides: Essential role of pkaR4 |
title_short |
Protein kinase A regulatory subunit isoforms regulate growth and differentiation in Mucor circinelloides: Essential role of pkaR4 |
title_full |
Protein kinase A regulatory subunit isoforms regulate growth and differentiation in Mucor circinelloides: Essential role of pkaR4 |
title_fullStr |
Protein kinase A regulatory subunit isoforms regulate growth and differentiation in Mucor circinelloides: Essential role of pkaR4 |
title_full_unstemmed |
Protein kinase A regulatory subunit isoforms regulate growth and differentiation in Mucor circinelloides: Essential role of pkaR4 |
title_sort |
protein kinase a regulatory subunit isoforms regulate growth and differentiation in mucor circinelloides: essential role of pkar4 |
publishDate |
2012 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15359778_v11_n8_p989_Ocampo http://hdl.handle.net/20.500.12110/paper_15359778_v11_n8_p989_Ocampo |
work_keys_str_mv |
AT ocampojosefina proteinkinasearegulatorysubunitisoformsregulategrowthanddifferentiationinmucorcircinelloidesessentialroleofpkar4 AT morenodecolonnasilvia proteinkinasearegulatorysubunitisoformsregulategrowthanddifferentiationinmucorcircinelloidesessentialroleofpkar4 AT rossisilviagraciela proteinkinasearegulatorysubunitisoformsregulategrowthanddifferentiationinmucorcircinelloidesessentialroleofpkar4 |
_version_ |
1768543625759686656 |