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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Autores principales: Ocampo, J., McCormack, B., Navarro, E., Moreno, S., Garre, V., Rossi, S.
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Acceso en línea:http://hdl.handle.net/20.500.12110/paper_15359778_v11_n8_p989_Ocampo
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spelling todo:paper_15359778_v11_n8_p989_Ocampo2023-10-03T16:21:43Z Protein kinase A regulatory subunit isoforms regulate growth and differentiation in Mucor circinelloides: Essential role of pkaR4 Ocampo, J. McCormack, B. Navarro, E. Moreno, S. Garre, V. Rossi, S. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar 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, J.
McCormack, B.
Navarro, E.
Moreno, S.
Garre, V.
Rossi, S.
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.
format JOUR
author Ocampo, J.
McCormack, B.
Navarro, E.
Moreno, S.
Garre, V.
Rossi, S.
author_facet Ocampo, J.
McCormack, B.
Navarro, E.
Moreno, S.
Garre, V.
Rossi, S.
author_sort Ocampo, J.
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
url http://hdl.handle.net/20.500.12110/paper_15359778_v11_n8_p989_Ocampo
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