A proteomic interrogation of Cryptococcus neoformans: interaction networks for calcineurin in a heated environment

Abstract

Evaluation of: Kozubowski L, Thompson JW, Cardenas ME, Moseley MA, Heitman J. Association of calcineurin with the COPI protein Sec28 and the COPII protein Sec13 revealed by quantitative proteomics. PLoS One 6(10), e25280 (2011).

Calcineurin (CN) is a calcium- and calmodulin-dependent protein phosphatase that consists of a catalytic subunit (calcineurin A [CnA]) and a calcium-binding, regulatory subunit (calcineurin B [CnB]). Calcineurin has been shown to be involved in a number of cellular processes, and aberrant signaling has been linked to multiple human diseases, such as cardiac hypertrophy and diabetes. Recent studies demonstrated that CN was involved in the survival of Cryptococcus neoformans, a fungal pathogen that infects humans, especially patients who are immunocompromised. CN appears to be essential for the survival and virulence of C. neoformans; however, the underlying mechanisms remain largely unknown. The Heitman laboratory recently identified a group of potential CnA-interacting proteins in C. neoformans during heat stress, and demonstrated an interaction of CnA with Sec28 and Sec13, which represent COPI and COPII protein complex members, respectively. The COP protein complexes are key proteins involved in intracellular endoplasmic reticulum and golgi protein trafficking. The results from the Heitman group suggest that CN interacts with components of the endoplasmic reticulum and the golgi during heat stress in C. neoformans and could highlight potential mechanisms by which these microbes could be targeted.

Keywords::

• calcineurin
• calmodulin
• coatomer proteins
• mass spectrometry
• protein–protein interaction

Financial & competing interests disclosure

Work in the authors’ laboratories was supported by the Heart and Stroke Foundation of Ontario (grants #T-6281 and #T-5042), the Canadian Institutes of Health Research (MOP-84267), the Canadian Foundation for Innovation, the Heart and Stroke/Richard Lewar Centre of Cardiovascular Excellence and an unrestricted grant from Boehringer Ingelheim (Canada). AO Gramolini is a Canada Research Chair. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.