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becomes the thermodynamically preferredstate. But the transformation first requires agerm of the crystal, a crystallite, to form. Suchcrystallites are created spontaneously as a resultof the incessant jiggling around of molecules in the liquid, caused by thermal fluctuations.However, most of the crystallites dissolve backinto the liquid. To grow, crystallites must over-come the barrier posed by surface tension —the unfavourable interactions between mol-ecules in the crystalline arrangement and thosein the surrounding liquid. A large enough crys-tallite that can overcome the barrier is termedthe critical nucleus; the process by which itforms is called nucleation. Once formed, thecritical nucleus will grow irreversibly and icewill form.

Water can be supercooled because crystalnucleation and growth may take a long time.But the processes become faster as the temper-ature falls, and they can be accelerated furtherby solid particles that act as a substrate forcrystal nucleation. This is known as hetero-geneous nucleation. It is of particular impor-tance in the atmosphere, where water exists assmall droplets that are suspended alongsideparticles that may act as heterogeneous icenuclei. These nuclei may either be immersedin the bulk of the water droplet, or come intocontact with the droplet surface.

Shaw and co-workers have examined thephenomenon of contact nucleation in labexperiments. As discussed in the first paper1,they set out to compare the efficiency of an icenucleus in causing crystallization when it isimmersed in the droplet and when it is in con-tact with the droplet’s surface. They used anexperimental set-up in which the same drop ofwater, with the same ice nucleus immersed orin contact, is repeatedly cooled and heatedhundreds of times. During each cooling run, they recorded the temperature at whichthe droplet froze. The result is an estimate ofthe most likely temperature at which droplets

freeze, which in turn is a measure of the effi-ciency of the particular nucleation mechanism.

They find that the freezing temperaturewhen the ice nucleus is in contact with thedroplet is about 5 °C higher than when it isimmersed in the droplet, showing that contactnucleation is a more effective mechanism thanimmersion nucleation. This conclusion is con-sistent with previous data. But the new resultsshow that the efficacy of contact nucleation isnot caused by transient effects related to an ice nucleus coming into contact with a waterdroplet, such as mechanical disturbance dueto collision, or to the dissolution of part of theice nucleus. Instead, it has simply to do withthe fact that the nucleus is in contact with thedroplet surface. This is a useful distinction,which may also be related to a proposal3 thathomogeneous nucleation (nucleation withoutan ice nucleus) is most effectively initiated atthe droplet surface.

In the second paper2, Durant and Shaw

describe a variation of the experiment inwhich the ice nucleus is initially immersed inthe droplet, but in conditions under which thedroplet slowly evaporates as it is cooled andheated. The nucleus then eventually comesinto contact with the surface of the droplet, butthis time from inside the droplet (Fig. 1). Inthis situation, too, the authors observe a rise inthe freezing temperature.

This ‘contact nucleation inside-out’ is evi-dently an efficient nucleation mechanism. Butis it of special significance? Yes, claim theauthors. They suggest that it may account forthe high rates of ice nucleation in wave clouds(Fig. 2), when the cloud droplets are evaporat-ing at temperatures that are too high for therates to be explained by homogeneous nucle-ation. Re-examination of existing observa-tional data may provide support for this idea.

Shaw and colleagues’ results1,2 will need tobe validated, but they are appealing in theirclarity and possible relevance to ice nucleationin the atmosphere. Extension of the experi-ments, perhaps with a clever choice of icenuclei and varying droplet sizes, may also pro-vide further evidence about homogeneoussurface nucleation4. Another route forwards isthrough computer simulations, which haveprovided insight into heterogeneous nucle-ation5 and homogeneous crystal nucleation inwater6. Such simulations could be extended toprovide a fresh angle on homogeneous andheterogeneous nucleation at surfaces. ■

Srikanth Sastry is at the Jawaharlal Nehru Centre for Advanced Scientific Research,Bangalore 560064, India.e-mail: sastry@jncasr.ac.in

1. Shaw, R. A., Durant, A. J. & Mi, Y. J. Phys. Chem. B 109,9865–9868 (2005).

2. Durant, A. J. & Shaw, R. A. Geophys. Res. Lett. 32,doi:10.1029/2005GL024175 (2005).

3. Tabazadeh, A., Djikaev, Y. S. & Reiss, H. Proc. Natl Acad. Sci.USA 99, 15873–15878 (2002).

4. Kay, J. E. et al. Atmos. Chem. Phys. Discuss. 3, 3361–3372(2003).

5. Cacciuto, A. et al. Nature 428, 404–406 (2004). 6. Matsumoto, M. et al. Nature 416, 409–413 (2002).

Figure 2 | Ice nucleation in wave clouds. Wave clouds — shown here — form when air is lifted up overa mountain, and water vapour in the upper reaches of the air current condenses to form water droplets.As the air current descends, the condensed water evaporates. Such an air current can bounce up anddown, and with condensation at the crests of such undulations a wave-like cloud pattern can emerge.Durant and Shaw2 argue that ‘contact nucleation inside-out’ may explain the extent of ice formationoccurring in the downwind region of such currents.

CELL BIOLOGY

Relays at the membraneRoel Nusse

The Wnt signalling pathway is a major route by which the cell conveysinformation from its exterior to the nucleus. A gap in the sequence ofsignalling proteins has now been filled.

The process of signal transduction allows a cellto receive messages from its environment andtransfer this signal from the membranethrough the cytoplasm and into the nucleus.Here the signal alters the expression of the various genes that contribute to the cell’sresponse. Regardless of the signal’s nature, thegeneral logic of the transduction pathways that

are triggered by protein ligands is roughly thesame. The signalling protein binds to a recep-tor on the cell’s surface, which consequentlyundergoes a conformational change. Com-monly, the receptor is then tagged with a phosphate group by an associated proteinkinase enzyme. The phosphorylation allowsthe receptor to recruit cytoplasmic signalling

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components that initiate a cascade of eventsresulting in changes in gene expression. Twopapers in this issue1,2 show that signal trans-duction initiated by the protein Wnt — amajor regulator of developmental processes —follows a similar strategy but with some inter-esting new twists.

Compared with other signalling cascades,the Wnt pathway3 is exceptional in its com-plexity, with numerous components and intri-cacies that go beyond this short overview. Oneof the key players in the pathway is �-catenin,a protein that resides in the cytoplasm and,once activated, is responsible for relaying thesignal into the nucleus. When cells are notexposed to Wnt, �-catenin is destined to bedestroyed (Fig. 1a). This process is triggered byphosphorylation of �-catenin, catalysed by theprotein kinase GSK3 and assisted by the �-catenin-binding partners Axin and APC.The Wnt signal activates two membranereceptors, the Frizzled and LRP6 molecules,which form a complex and trigger signalling to the cytoplasm that halts the breakdown of �-catenin4. But how are the events at thereceptor level coupled to �-catenin, and howdoes �-catenin escape degradation?

The discovery, several years ago, that theAxin protein can bind to the cytoplasmic tail of the LRP6 receptor5, provided a mechanismby which Axin is seized from �-catenin6. Thischanges the fate of �-catenin: instead of beingdestroyed, it accumulates and enters thenucleus, where it executes a programme ofWnt-induced gene expression (Fig. 1b). Cru-cially, the binding of Axin to the LRP6 tail ispromoted by phosphorylation of LRP6 (ref. 7),suggesting that protein kinases must be re-cruited to the receptor after activation by Wnt8.

The identity of these kinases is the subjectof the papers by Zeng et al. (page 873 of thisissue)1 and Davidson et al. (page 867)2. Toappreciate their function, some detail is nec-essary. Phosphorylation of LRP6 occurs onseveral clusters of serines and threonines, with a central proline-rich motif (PPPSP) as a hallmark (Fig. 1b; inset). As in many othercases of cluster phosphorylation, there is apriming phosphorylation event after whichthe remaining residues become modified as well. Proline-rich environments are con-ducive to phosphorylation by GSK3, so Zenget al.1 tested the PPPSP motif on LRP6 foractivity. They found that the serine in themotif is indeed modified by GSK3, leading to activation of signalling. Strikingly, GSK3 is now known to phosphorylate a number of Wnt signalling components, including �-catenin, Axin and APC. GSK3 used to bethought of as a negative component in Wntsignalling: when it was deleted genetically,Wnt-response genes were activated because�-catenin was no longer phosphorylated ordegraded. But we now know that it acts posi-tively on LRP6, activating Wnt signalling —an effect missed in the genetic experimentsbecause of its negative involvement furtherdown the pathway.

Residues next to the PPPSP motif also getphosphorylated. What is the enzyme? Basedon an expression screen, Davidson et al.2

identify this kinase as a member of the CK1family, CK1�. Beyond biochemical experi-ments showing that CK1 can phosphorylatethe LRP6 tail, Davidson et al. demonstrate that the gene encoding CK1� is required for Wntsignalling to occur, and that overexpression ofthis gene is sufficient to activate the pathway.

As with GSK3, the diminutive name CK1 doesnot do justice to the numerous functions of theCK1 family in cell physiology. Within thisfamily, CK1� is an outlying relative, and, inter-estingly, it has a membrane anchor in the formof a fatty-acid attachment site. Eliminating thefatty-acid anchor domain from CK1� resultsin loss of Wnt signalling, implying that thiskinase needs to be associated with the mem-brane to act.

So now there are two LRP6 kinases, raisingthe question of how these enzymes becomeactivated by the Wnt signal. Here the twopapers differ in their conclusions. Zeng et al.suggest that the GSK3-dependent phosphory-lation of the PPPSP motif is induced by Wnt.By contrast, Davidson et al. conclude thatPPPSP is usually phosphorylated in cells, inthe absence of Wnt; that is, it is constitutivelyphosphorylated. They propose that it is thesubsequent modification of neighbouringresidues, catalysed by CK1�, that is dependenton the Wnt signal. This discrepancy needs tobe resolved, but if phosphorylation of LRP6 byGSK3 is indeed signal dependent, it would bean exception to the general rule that GSK3activity is constitutive in cells. GSK3 isinvolved in many signalling pathways, but itacts on all its multitude of targets withoutbeing triggered by a signal from outside. Bycontrast, CK1� activity is clearly stimulated byWnt signalling, as adding Wnt protein to cellsleads to modification within a few minutes.

There are many questions remaining. Forexample, it is not known how CK1� activity isregulated or whether the enzyme becomesphysically associated with LRP6. Because of its unique function, this enzyme provides an attractive novel target for Wnt-specificinhibitors.

When we now compare Wnt signallingevents at the receptor level to other signallingpathways, there are many parallels but one dif-ference. In the Wnt signalling pathway, ligandbinding triggers the formation of a receptorcomplex, and protein kinases modify thereceptor tails, leading to recruitment of cyto-plasmic factors. In other signalling pathways,however, receptor-induced protein phosphory-lation amplifies the signal, and the receptor-associated kinase acts as a catalyst for themodification of many substrate molecules. Inthis regard, Wnt signalling is peculiar: Wnt-induced LRP6 phosphorylation acts by titrat-ing away a negative regulator of signalling,Axin. This implies a stoichiometric rather thana catalytic mechanism of signal transduction.On the other hand, Axin is present in very lowconcentrations in cells, much lower than theother components in the �-catenin destruc-tion complex9. So, is it possible that Axin actu-ally plays a dynamic role, shuttling betweenthe receptor and the destruction complex andacting as an amplifier of Wnt signalling ratherthan as a simple scaffold? ■

Roel Nusse is in the Howard Hughes MedicalInstitute, Department of Developmental Biology,

Figure 1 | Crucial kinases. a, In cells not activated by Wnt, a complex between �-catenin, Axin, APCand GSK3 causes phosphorylation of �-catenin and its consequent destruction. The Wnt receptorsLRP6 and Frizzled are unoccupied. b, Without Axin, �-catenin is stabilized and it enters the nucleus tocontrol gene expression. Inset, binding of Wnt to cells results in phosphorylation (P) of LRP6 residuesin its cytoplasmic tail. Zeng et al.1 and Davidson et al.2 show that this is catalysed by the GSK3 andCK1� protein kinases. CK1� is attached to the membrane by a lipid anchor domain. Several other siteson LRP6 that become phosphorylated are not shown here. The phosphorylated LRP6 recruits Axin,removing it from the �-catenin destruction complex and stabilizing �-catenin.

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Beckman Center, Stanford University, Stanford,California 94305-5329, USA.e-mail: rnusse@stanford.edu

1. Zeng, X. et al. Nature 438, 873–877 (2005).2. Davidson, G. et al. Nature 438, 867–872 (2005).3. Logan, C. & Nusse, R. Annu. Rev. Cell Dev. Biol. 20, 781–810

(2004).

repeater is no use in the quantum regime: it ismuch too noisy, and creates so many errorsthat any quantum key being transmittedwould not survive. To put the problem in more quantum-mechanical terms, a classicalrepeater breaks down quantum entanglement.This delicate phenomenon is associated with very strong, non-classical correlationsbetween the states of two widely separatedqubits, and is a crucial element of all quantumcommunication schemes: in effect, it allowsany useful qubit to be ‘teleported’ directly to itsdestination, avoiding transmission losses3.

So quantum communication must re-invent the repeater concept, using quantumhardware that preserves coherence. This isfeasible in principle4: a quantum repeaterwould be nothing more than a small quantumprocessor. The exact number of qubits thatwould have to be stored and processed in sucha repeater to ensure high-fidelity quantumcommunication over thousands of kilometresis an open issue. But it is likely to be in the

range of tens or hundreds — much lower than the number required for a fully fledgedquantum computer. The proposal in 2001 ofthe so-called DLCZ quantum informationprotocol5, in which an ensemble of manyatoms stores just one qubit, was a significantstep towards a functioning quantum repeater.This protocol uses a process known as spon-taneous Raman scattering, in which an inci-dent photon is scattered inelastically (that is,with a change in its frequency) between twoatomic ground states.

Chanelière et al.1 and Eisaman et al.2 exploitthe DLCZ protocol to set up a controllablesingle-photon source for further experimen-tation. After initially preparing all the atomsof an ensemble in one ground state, a weaklaser pulse (which nevertheless contains manyphotons) is used to induce a Raman transitionof just one atom within the ensemble. As aconsequence, a single spontaneous Ramanphoton is scattered, and its detection heraldsthe creation of a collective, delocalized, single-atom excitation of the ensemble. This excita-tion can be stored for as long as all the atomiclevels in the sample maintain a constant phaserelationship (a period known as the coherencetime of the ensemble). This excitation can beconverted back into a single-photon light field of controllable direction, intensity andfrequency using another pump pulse (for areview of recent experimental work in thisarea, see ref. 6).

Once a single photon has been generated,the second stage is to catch it, and then releaseit again, in a second, remote atomic ensemble.The trick here is to use a second atomicensemble that is opaque to the photon —absorbing rather than transmitting it — andthat can only be made transparent by using anextra laser beam. This transparency arisesthrough a neat and extensively studied inter-ference phenomenon, electromagneticallyinduced transparency (EIT). If the EIT laser

QUANTUM INFORMATION

Remember that photonPhilippe Grangier

Storing single photons in atomic memories, and releasing them at a latertime, is a required step on the way to quantum repeaters and long-distancequantum cryptography networks. This step has now been taken.

The basic unit of quantum information, thequantum bit or qubit, can be encoded in vari-ous physical quantities, such as the polariza-tion states of photons, or the spin states ofatomic nuclei. To make qubits practically use-ful, random coupling of them with the exter-nal world — an effect known as decoherence— must at all costs be avoided or corrected.This makes photons (the quanta of light) par-ticularly suitable for qubit transmission, asthey can travel over very long distances withvery little decoherence. For qubit storage,encoders such as atoms come into their own:they can be kept in ‘traps’ for long periods,again avoiding deleterious decoherence effectsfrom outside.

In experiments detailed in two papers inthis issue, Chanelière et al. (page 833)1 andEisaman et al. (page 837)2 contrive to combinethe two crucial aspects of transport and stor-age: they generate a single photon on demand,catch it and store it in a remote atomic mem-ory, and release it some time later. The advanceis potentially highly significant for the field ofquantum cryptography, also known as quan-tum key distribution (QKD). This emergingtechnology promises absolutely secure trans-mission of the key codes that are essential todecipher any encrypted message (Box 1).

Previous advances in quantum key distrib-ution have owed much to the fact that photonsthat are used to encode the keys are very goodqubit carriers: apart from maintaining a robustquantum state throughout transmission, theycan be detected efficiently and with low levelsof noise. But light signals cannot — whetherviewed classically or quantum-mechanically— propagate over infinite distances in opticalfibres. They are in fact dampened exponen-tially with distance: by a factor of two over 15kilometres, and by a factor of a hundred over100 kilometres. In classical optical telecom-munications, this problem is solved by usingsimple, readily available devices known asrepeaters, which can amplify and reshape thetransmitted signal. But a good classical

The purpose of quantum key distribution is toshare a secret key among legitimate users thatallows them and only them to decode messages.Some sort of key that allows a message to bedeciphered is essential to all forms of encryption.Common, classical schemes used in electroniccommerce can set up a key by relying oncomputationally difficult problems, such as the splitting of a very large number into twoprime-number factors, that are in fact — givenunlimited patience and computational power —breakable.

The only totally secure classical encryptionsystem is the ‘one-time pad’, which uses a keythat is as long as the message itself and that maybe used only once. This solution leads to what isknown as the key distribution problem: as the keymust be transmitted between sender andrecipient, it is itself susceptible to interception byan eavesdropper. In the classical world, someone

can listen in on such a signal passively withoutchanging the bits that make it up at all, so neithersender nor recipient need ever know that theircommunication has been intercepted.

Not so in the world of quantumcommunication. Qubits do not possess definitevalues such as the 0 or 1 of classical bits; rather, they represent a so-called coherentsuperposition of physical states such as thepolarizations of a photon. A fundamental featureof quantum mechanics is that the mere act ofobserving such a superposition will cause it to‘collapse’ into a definite state. This means anyattempt by an eavesdropper to intercept a keymade of qubits can be easily spotted by senderand recipient. Given this knowledge, and as long as the errors created by the eavesdropper(or any other perturbation) are not too large, it should be possible to build up an errorless andperfectly secure key. P.G.

Box 1 | Key codes: classical versus quantum cryptography

4. Cong, F., Schweizer, L. & Varmus, H. Development 131,5103–5115 (2004).

5. Mao, J. et al. Mol. Cell 7, 801–809 (2001).6. Tolwinski, N. S. et al. Dev. Cell 4, 407–418 (2003).7. Tamai, K. et al. Mol. Cell 13, 149–156 (2004).8. He, X., Semenov, M., Tamai, K. & Zeng, X. Development 131,

1663–1677 (2004).9. Lee, E., Salic, A., Kruger, R., Heinrich, R. & Kirschner, M. W.

PLoS Biol. 1, E10 (2003).

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