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Protein kinase A regulatory subunit isoforms regulate growth and differentiation in Mucor circinelloides: essential

J Ocampo1, B McCormack, E Navarro

  • 1Departamento de Química Biológica, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, Argentina.

Eukaryotic Cell
|May 29, 2012
PubMed

Insights

Four regulatory subunits of protein kinase A (PKA) in Mucor circinelloides control growth and differentiation. PKAR4 is essential, impacting germ tube emergence, while other isoforms regulate sporulation and cell volume.

Area of Science:

  • Mycology
  • Molecular Biology
  • Biochemistry

Background:

  • The cyclic AMP (cAMP)-protein kinase A (PKA) pathway regulates crucial cellular processes.
  • In the dimorphic fungus Mucor circinelloides, PKA holoenzyme comprises catalytic and regulatory (R) subunits.
  • Four R subunit isoforms (PKAR1-4) exist in M. circinelloides.

Purpose of the Study:

  • To elucidate the specific roles of each PKA regulatory subunit isoform in M. circinelloides.
  • To investigate the impact of these isoforms on fungal growth, differentiation, and dimorphism.

Main Methods:

  • Construction and analysis of null mutants for each PKAR isoform.
  • Assessment of fungal growth, germ tube emergence, sporulation, and cell volume.
  • Analysis of mRNA and protein levels to understand differential regulation.
  • Investigation of post-translational modifications like ubiquitylation.

Main Results:

  • PKAR4 is essential for M. circinelloides viability, with its absence impeding germ tube emergence.
  • PKAR2 null mutants exhibit accelerated germ tube emission and can germinate anaerobically.
  • Other isoforms (PKAR1, PKAR3) display distinct alterations in growth and differentiation.
  • Differential expression and post-translational modification (ubiquitylation of PKAR1/2) indicate complex regulatory mechanisms.

Conclusions:

  • Each PKAR isoform plays a unique role in M. circinelloides physiology.
  • The isoforms contribute to the specificity of the cAMP-PKA pathway and control fungal dimorphism.
  • Differential regulation of R subunits ensures precise control over growth and differentiation processes.

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