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cross-sectional area of the pore, clearly sug-gests that the observed conformation is an intermediate stage on its way to the open state. Indeed, the observed tilts of the helices match remarkably well with those predicted by spec-troscopic studies of channels trapped in the open state10.
Perhaps the most surprising result of this work6 is that, defying all expectations, the channel is arranged as a tetramer, not a pen-tamer as observed for the crystal structure of TbMscL in a closed state8. This is in contrast to the vast majority of oligomeric membrane proteins, each of which maintains the same oligomeric architecture across species and physiological states, at least for those studied so far. Still, controversy regarding the oligo-meric state of MscL is not new — it was origi-nally thought to be a hexamer, on the basis of biochemical experiments15 and electron-crystallography data16. It is, however, unlikely that the present result6 will lend further support to the idea that MscL gating is the consequence of monomer aggregation in the plane of the bilayer (which could support variable oligomeric states).
The observed tetrameric structure of trun-cated SaMscL raises several questions. Does the oligomeric state of MscL vary in different species? Does the channel reside in the mem-brane as different multimers? If so, does each multimer have different functional properties? And are particular multimers favoured by par-ticular physiological conditions? Regardless of the answers, the plasticity of this family of ion channels seems to be exceptional. More
time and experimental insight will surely be needed to realize the full implications of this structure6. ■
Valeria Vásquez is in the Department of
Molecular and Cellular Physiology, Stanford
University School of Medicine, Stanford,
California 94305, USA. Eduardo Perozo is in
the Department of Biochemistry and Molecular
Biology, University of Chicago, Chicago,
Illinois 60637, USA.
e-mail: [email protected]
1. Broder, S. & Venter, J. C. Annu. Rev. Pharmacol. Toxicol. 40, 97–132 (2000).
2. Anishkin, A. & Kung, C. Curr. Opin. Neurobiol. 15, 397–405
(2005).
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Miller, S. Nature Rev. Microbiol. 5, 431–440 (2007).
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5. Martinac, B., Saimi, Y. & Kung, C. Physiol. Rev. 88, 1449–
1490 (2008).
6. Liu, Z., Gandhi, C. S. & Rees, D. C. Nature 461, 120–124
(2009).
7. Wiggins, P. & Phillips, R. Biophys. J. 88, 880–902
(2005).
8. Chang, G., Spencer, R. H., Lee, A. T., Barclay, M. T. & Rees,
D. C. Science 282, 2220–2226 (1998).
9. Sukharev, S. I., Sigurdson, W. J., Kung, C. & Sachs, F. J. Gen.
Physiol. 113, 525–540 (1999).
10. Perozo, E., Cortes, D. M., Sompornpisut, P., Kloda, A. &
Martinac, B. Nature 418, 942–948 (2002).
11. Sukharev, S., Betanzos, M., Chiang, C. S. & Guy, H. R. Nature
409, 720–724 (2001).
12. Cruickshank, C. C., Minchin, R. F., Le Dain, A. C. &
Martinac, B. Biophys. J. 73, 1925–1931 (1997).
13. van den Bogaart, G., Krasnikov, V. & Poolman, B. Biophys. J.
92, 1233–1240 (2007).
14. Betanzos, M., Chiang, C. S., Guy, H. R. & Sukharev, S. Nature
Struct. Biol. 9, 704–710 (2002).
15. Sukharev, S. I., Schroeder, M. J. & McCaslin, D. R. J. Membr.
Biol. 171, 183–193 (1999).
16. Saint, N. et al. J. Biol. Chem. 273, 14667–14670
(1998).
NITROGEN CYCLE
Oceans apart Maren Voss and Joseph P. Montoya
Reactive nitrogen is lost from the oceans as dinitrogen — N2 — produced by microbial metabolism. The latest twist in an ongoing story is that different pathways dominate in two of the oceanic regions concerned.
The availability of nitrogen limits biological production in much of the world ocean1; this in turn affects the strength of the ‘biologi-cal pump’ that converts carbon dioxide into organic matter that can sink and be seques-tered in the deep sea2. The main input to the marine nitrogen cycle comes from the fixation of nitrogen gas (N2) into biologically available forms. The main output is through biological processes that generate a return flux of N2. Both input and output remain poorly con-strained1, and there is a pressing need to define them better.
On page 78 of this issue, Ward et al.3 describe how they have investigated the output side of the budget. They report on a comprehensive field study aimed at identifying the processes
and organisms responsible for N2 production in two of the major sites of nitrogen loss in the world ocean. The sites concerned are the oxy-gen minimum zones (OMZs) of the Arabian Sea and the Eastern Tropical South Pacific (ETSP). At these sites, microbial degradation of sinking organic matter obtained by primary production — mainly photosynthesis — in the surface ocean completely removes oxygen from large parts of the water column. The result-ing conditions favour metabolic pathways that convert nitrogen from its biologically reactive forms (for example, nitrate and ammonium) to N2.
In one of the N2-conversion pathways, termed heterotrophic denitrification, nitrate acts as a terminal electron acceptor in microbial
respiration; this was long viewed as the main metabolic pathway for N2 production in midwater OMZs. But the picture was com-plicated by the discovery that another route — anammox, a pathway that produces N2 by coupling the reduction of nitrite to the oxida-tion of ammonium — has an important role in the oceanic nitrogen cycle4,5. The autotrophic microbes in this pathway produce biomass from inorganic molecules by harvesting energy from the anammox reaction. Both pathways are shown in Figure 1, which summarizes the overall marine nitrogen cycle.
Studies in the Black Sea5, the Benguela upwelling system6 and the ETSP7 suggested that anammox may in fact be the dominant pathway removing reactive nitrogen from the ocean. If so, however, what supplies the nec-essary substrates? Heterotrophic denitrifica-tion can potentially do so — it can supply both nitrite, an intermediate in the denitrification pathway, and ammonium, a product of hetero-trophy, to support anammox4. Earlier this year, however, Lam et al.7 suggested a major revision of the nitrogen cycle in which a process called dissimilatory nitrate reduction to ammonium (DNRA) provides the necessary ammonium for anammox. In this revised cycle, hetero-trophic denitrification has a minor role and is no longer a significant source of N2.
Part of the uncertainty surrounding hetero-trophic denitrification is due to the difficulty of measuring the rates of the processes involved. Even low levels of oxygen contamination sup-press the activity of denitrifying microbes, and the high concentration of N2 in the water greatly reduces the sensitivity of experimental methods that are based on following the move-ment of the 15N isotope tracer into the N2 pool.
Figure 1 | Principal features of the marine nitrogen cycle. 1, Anammox, involving the generation of N2 from inorganic constituents by autotrophic microbes. 2, Nitrogen fixation. 3, Nitrification. 4, Heterotrophic denitrification, in which N2 is produced from NO3
− used in microbial respiration of organic substrates; this process also results in the production of NH4
+ and CO2 (not shown). 5, Dissimilatory nitrate reduction to ammonium (DNRA). NO3
−, nitrate; NO2−, nitrite; N2O, nitrous oxide;
NH4+, ammonium. The N2-output pathways,
1 and 4, were the subject of Ward and colleagues’ study3.
NO3–
NO2–
NO2–
N2O
N2O
N2
NH4+
NH4+
1
21
3
4
Primaryproducers
Heterotrophs
Assimilation Excretion
Assimilation
5 34
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Ward et al.3 have overcome these difficulties by carrying out a set of experiments designed to evaluate the relative prevalence of hetero-trophic denitrification and anammox.
Their main result is that the DNRA–anam-mox nitrogen cycle does not have a major role in the Arabian Sea (Fig. 2a), the largest of the world’s three OMZs. Ward et al. show convinc-ingly that it is indeed heterotrophic denitrifi-cation that accounts for most of the nitrogen losses in this system. By contrast, they meas-ured much lower rates of denitrification in the ETSP (Fig. 2b), a finding consistent with the core argument of Lam and colleagues7. In both the Arabian Sea and the ETSP, however, the authors’ molecular data3 showed the pres-ence of heterotrophic denitrifiers in the water column at much higher abundances than the anammox organisms. This raises the obvious questions of why the strength of heterotrophic denitrification differs so much between the two OMZs, and which factors promote deni-trifier activity in the Arabian Sea and not in the ETSP.
There is now strong evidence that hetero-trophic denitrification does have a central role in removing reactive nitrogen from the ocean. But we still lack a clear understanding of why it is so much more important in the Arabian Sea. Ward et al.3 suggest that a difference in the magnitude and timing of the supply of organic matter to the OMZ is the critical factor. Indeed, the Arabian Sea seems to be more productive on average8, and it is known to support large blooms of nitrogen-fixing organisms9 that intro-duce extra biomass into the surface waters. By contrast, production in the ETSP may be more episodic. During periods of increased delivery
Figure 2 | Two oceans, two nitrogen cycles. Outlines of nitrogen cycling in the oxygen minimum zones of (a) the Arabian Sea and (b) the Eastern Tropical South Pacific (ETSP). Teardrops show typical profiles of concentration as a function of depth; PON, particulate organic nitrogen. Blue lines denote pathways related to the anammox–DNRA cycle; white lines are related to heterotrophic denitrification. 1, Anammox; 2, remineralization; 3, nitrate reduction; 4, heterotrophic denitrification; 5, DNRA. As Ward et al. show3, in the Arabian Sea denitrification is much more important than anammox in generating loss of nitrogen from the system as N2. In the ETSP, anammox is fuelled by ammonium from DNRA and is an important route to N2.
NO3–
NO2– N2 NH4
+NO2– N2 NH4
+
NO3–
ETSPArabian Sea ba
Inc
rea
sing
wa
ter d
ep
th
12
3 4
5
3
12
3 4
5
3
O2 PONO2 PON
of organic matter to the OMZ, processes in the ETSP may more closely resemble those in the Arabian Sea, a possibility that can be tested only through additional studies at sea.
The workings of the oceanic nitrogen cycle may seem arcane, but understanding them is a necessary component in understanding both global marine productivity and climate change. The two major pathways to N2 — heterotrophic denitrification and anammox — each reduce the ocean’s stock of reactive nitrogen, but with
NEUROSCIENCE
Persistent feedbackHyojung Seo and Daeyeol Lee
How does the brain remember the consequences of our actions? Persistent activity in the prefrontal cortex and basal ganglia may be crucial for learning correct actions through experience.
Do you jump out of bed when you hear the alarm clock ring in the morning? Or do you push the snoozer? Your choice will depend on the consequences of similar actions in the past. Typically, if an action triggered by a stimulus leads to a pleasant outcome, such as food or safety, we are more likely to perform the same action on re-encountering the same stimulus1. Therefore, a fundamental building block in shaping behaviour is the relationship between a sensory event, a chosen action and its consequences, but how the brain stores this information is still a matter of speculation.
A recent paper in Neuron by Histed et al.2
sheds some light on these mechanisms by showing that neurons in the primate prefron-tal cortex and basal ganglia display persist-ent activity that is related to the outcomes of previous actions.
The task of forming an association between a particular sensory event, a behavioural response and the outcome of this response (Fig. 1) is not trivial, as a particular outcome might be preceded by multiple sensory stim-uli and responses. To discover which of these events are related, it is often necessary to
different collateral effects. Denitrification is a significant source of nitrous oxide (N2O)10, a greenhouse gas, and its heterotrophic nature makes it a potential short-circuit in the bio-logical pump that transfers carbon from the atmosphere into the deep sea. By contrast, anammox produces no greenhouse gases, and is an autotrophic process that can potentially increase the efficiency of the biological pump by reducing the net production of CO2 within the water column. Shifts in the productivity of the oceans due to rising temperatures and lev-els of CO2 are likely to affect the distribution and extent of OMZs11. Knowing which nitro-gen-cycle pro cesses are at work, and where, will be an essential aspect of gauging the likely response of the oceans to global-scale changes in temperature and CO2. ■
Maren Voss is at the Leibniz Institute for Baltic
Sea Research, Warnemünde, Seestrasse 15,
D-18119 Rostock, Germany. Joseph P. Montoya
is in the School of Biology, Georgia Institute of
Technology, Atlanta, Georgia 30332, USA.
e-mails: [email protected];
1. Codispoti, L. A. Biogeosciences 4, 233–253
(2007).
2. Sabine, C. L. et al. Science 305, 367–371 (2004).
3. Ward, B. B. et al. Nature 461, 78–81 (2009).
4. Dalsgaard, T. et al. Nature 422, 606–608
(2003).
5. Kuypers, M. M. M. et al. Nature 422, 608–611 (2003).
6. Kuypers, M. M. M. et al. Proc. Natl Acad. Sci. USA 102, 6478–6483 (2005).
7. Lam, P. et al. Proc. Natl Acad. Sci. USA 106, 4752–4757
(2009).
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(eds Capone, D. et al.) 51–94 (Elsevier, 2008).
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(2008).
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