Editors' ChoiceTemperature Sensing

Going Outside When It’s Warm

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Science Signaling  21 Sep 2010:
Vol. 3, Issue 140, pp. ec286
DOI: 10.1126/scisignal.3140ec286

Integral membrane proteins that act as thermosensors can stimulate adaptive responses to changing temperatures. For instance, autophosphorylation of Bacillus subtilis DesK, which acts as a histidine kinase at cold temperatures, leads to the transcriptional activation of a gene that encodes an acyl lipid desaturase and thereby production of unsaturated fatty acids that promote membrane fluidity. But how does DesK know when to switch on this process? Cybulski et al. used substituted-cysteine accessibility method (SCAM) analysis to confirm the existence of four transmembrane (TM) helices predicted by membrane-topology bioinformatics and identify a fifth membrane-spanning domain (TM1) at the N terminus. In vivo analyses of the ability of DesK deletion variants to activate a reporter gene containing the desaturase promoter revealed that TM1 was critical for regulation of DesK activity: Activity of a mutant lacking TM1 was comparable to that of the unregulated cytoplasmic C-terminal fragment (DesKC, which contains the catalytic region). Moreover, a construct consisting of 17 residues of the TM1 N-terminal domain linked to the last 14 residues of the C-terminal TM5 domain, and thereby to DesKC, showed thermal regulation similar to that of wild-type DesK. Furthermore, this construct [the “minimal sensor region” (MS, the hybrid TM1-TM5 membrane-spanning segment) linked to DesKC (MS-DesKC)] showed temperature-dependent autophosphorylation when integrated into liposomes. The authors postulated that a cluster of hydrophilic amino acids (Glu9, Lys10, and Asn12) near the MS lipid-water interface might act as a molecular “sunken buoy” that was hydrated with membrane narrowing at high temperatures but lost hydration with membrane expansion at low temperatures. Consistent with this hypothesis, substitution of this cluster with hydrophobic amino acids blocked low temperature–dependent stimulation of desaturase transcription, whereas shifting Lys10 to position 11, or adding an additional lysine at position 11, increased MS-DesKC activity. Moreover, the autokinase activity of MS-DesKC in bilayers of phosphatidylcholines with monounsaturated fatty acyl chains of different length (20, 16, or 14 carbons) increased with chain length. The authors thus propose that thermosensing by DesK depends on its ability to monitor temperature-dependent changes in membrane thickness through the hydration of the sunken buoy motif; they speculate that membrane thickness could provide a more general cue for thermal sensitivity.

L. E. Cybulski, M. Martín, M. C. Mansilla, A. Fernández, D. de Mendoza, Membrane thickness cue for cold sensing in a bacterium. Curr. Biol. 20, 1539–1544 (2010). [PubMed]

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