Editors' ChoiceTransporters

New connections: Regulating transporters

Sci. Signal.  16 Aug 2016:
Vol. 9, Issue 441, pp. ec189
DOI: 10.1126/scisignal.aai7954

Multiple mechanisms exist to regulate the activity of proteins that function as transporters of molecules and ions across cellular and subcellular membranes to control the molecular composition and electrical properties of cells and subcellular compartments. Transporters play a key role in responses to various types of stress in all organisms, including bacteria, plants, and animals. In this issue of Science Signaling, Schuster et al. identified OpuCA, a component of the osmolyte uptake system OpuC, as a receptor for cyclic diadenosine monophosphate (c-di-AMP) in the opportunistic pathogen Staphylococcus aureus. Under conditions of osmotic stress, OpuC mediated the uptake of carnitine, but not other compatible solutes, to prevent water loss and promote cell survival. The bacterial second messenger c-di-AMP reduced OpuC-mediated carnitine uptake, thereby preventing inappropriate activity of this transporter. Understanding how bacteria cope with osmotic stress provides insight that could be leveraged to target pathogenic bacteria. Léran et al. added molecular details to the pathway that controls the activity of the plant nitrate sensor and transporter NPF6.3 (also known as NRT1.1). The calcium sensing protein CBL1 and the protein phosphatase ABI2, which is inhibited by the stress hormone abscisic acid, enhanced the activity of NPF6.3, suggesting a mechanism by which energy expensive processes of growth, nitrate uptake, and nitrate utilization may be coordinated with plant stress. In an example of the regulation of transporter function uptake in mammals, Raju et al. identified posttranslational regulation by S-nitrosylation of the astrocyte glutamate transporter GLT1 (also known as EEAT2) as a potential mechanism by which the gasotransmitter NO (nitric oxide) enhances glutamatergic neurotransmission by reducing clearance of glutamate. These studies illustrate some of the diverse mechanisms by which transporter activity can be regulated—direct binding of a regulatory ligand in c-di-AMP–mediated regulation of OpuCA, phosphorylation-dependent regulation in NPF6.3, and S-nitrosylation-mediated regulation of GLT1.

C. F. Schuster, L. E. Bellows, T. Tosi, I. Campeotto, R. M. Corrigan, P. Freemont, A. Gründling, The second messenger c-di-AMP inhibits the osmolyte uptake system OpuC in Staphylococcus aureus. Sci. Signal. 9, ra81 (2016). [Abstract]

S. Léran, K. H. Edel, M. Pervent, K. Hashimoto, C. Corratgé-Faillie, J. N. Offenborn, P. Tillard, A. Gojon, J. Kudla, B. Lacombe, Nitrate sensing and uptake in Arabidopsis are enhanced by ABI2, a phosphatase inactivated by the stress hormone abscisic acid. Sci. Signal. 8, ra43 (2015). [Abstract]

K. Raju, P.-T. Doulias, P. Evans, E. N. Krizman, J. G. Jackson, O. Horyn, Y. Daikhin, I. Nissim, M. Yudkoff, I. Nissim, K. A. Sharp, M. B. Robinson, H. Ischiropoulos, Regulation of brain glutamate metabolism by nitric oxide and S-nitrosylation. Sci. Signal. 8, ra68 (2015). [Abstract]

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