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Eukaryotic Cell, February 2008, p. 237-246, Vol. 7, No. 2
1535-9778/08/$08.00+0     doi:10.1128/EC.00079-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Amt2 Permease Is Required To Induce Ammonium-Responsive Invasive Growth and Mating in Cryptococcus neoformans{triangledown}

Julian C. Rutherford,1,{dagger} Xiaorong Lin,1,{ddagger} Kirsten Nielsen,1,§ and Joseph Heitman1,2*

Departments of Molecular Genetics and Microbiology,1 Medicine, Duke University Medical Center, Durham, North Carolina2

Received 14 March 2007/ Accepted 14 November 2007

The conserved AmtB/Mep/Rh family of proteins mediate the transport of ammonium across cellular membranes in a wide range of organisms. Certain fungal members of this group are required to initiate filamentous growth. We have investigated the functions of two members of the AmtB/Mep/Rh family from the pathogenic basidiomycete Cryptococcus neoformans. Amt1 and Amt2 are low- and high-affinity ammonium permeases, respectively, and a mutant lacking both permeases is unable to grow under ammonium-limiting conditions. AMT2 is transcriptionally induced in response to nitrogen limitation, whereas AMT1 is constitutively expressed. Single and double amt mutants exhibit wild-type virulence in two models of cryptococcosis. Consistent with this, the formation of two C. neoformans virulence factors, cell wall melanin and the extracellular polysaccharide capsule, is not impaired in cells lacking either or both of the Amt1 and Amt2 permeases. Amt2 is, however, required for the initiation of invasive growth of haploid cells under low-nitrogen conditions and for the mating of wild-type cells under the same conditions. We propose that Amt2 may be a new fungal ammonium sensor and an element of the signaling cascades that govern the mating of C. neoformans in response to environmental nutritional cues.

* Corresponding author. Mailing address: Room 322, CARL Building, Box 3546, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham NC 27710. Phone: (919) 684-2824. Fax: (919) 684-5458. E-mail: heitm001{at}duke.edu

{triangledown} Published ahead of print on 30 November 2007.

{dagger} Present address: Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom.

{ddagger} Present address: Department of Biology, Texas A&M University, College Station, TX.

§ Present address: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN.

Eukaryotic Cell, February 2008, p. 237-246, Vol. 7, No. 2
1535-9778/08/$08.00+0     doi:10.1128/EC.00079-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Dabas, N., Schneider, S., Morschhauser, J. (2009). Mutational Analysis of the Candida albicans Ammonium Permease Mep2p Reveals Residues Required for Ammonium Transport and Signaling. Eukaryot Cell 8: 147-160 [Abstract] [Full Text]  
  • Rutherford, J. C., Chua, G., Hughes, T., Cardenas, M. E., Heitman, J. (2008). A Mep2-dependent Transcriptional Profile Links Permease Function to Gene Expression during Pseudohyphal Growth in Saccharomyces cerevisiae. Mol. Biol. Cell 19: 3028-3039 [Abstract] [Full Text]  


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