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is believed to be well understood. But verydistant supernovae seem to be strikinglydimmer — and thus farther away — thanexpected. This suggests that, at large scales,the expansion of the Universe is accelerating,not slowing down; some mysterious repul-sive force is making the Universe fly apart.The puzzling thing, however, is that this newforce cannot possibly arise from either matteror radiation, because the gravitational forceexerted by such sources could only make theexpansion slow down (just as the Earth’sgravity slows a stone thrown into the air).

Perhaps the accelerating expansion is dueto the fact that gravity itself is modified atcosmologically large distances5. But if weassume that gravity remains ‘normal’ at rea-sonably large distances, then we are left withthe option that the Universe must be filledwith a mysterious source of gravity, whoseproperties are strikingly different from thoseof standard matter and radiation — darkenergy. To generate a repulsive gravitationalforce, the new source must have an unusual‘equation of state’ describing its behaviour,and must exert a large negative pressure.Also,as the Universe expands,the new sourcemust be diluted at a much slower rate thanany known form of matter or radiation.

What could this new, almost undilutablesource be? Apart from modified gravity, theonly such source considered until recentlywas the potential energy of a spatially uni-form, scalar (Bose–Einstein) condensate,known as quintessence6. This energy acts injust the same way as Einstein’s cosmologicalconstant, inducing the accelerated expan-sion of space. In particular, this observationis the basis of so-called inflationary cosmol-ogy — the commonly accepted cosmologicalparadigm for the early history of our Uni-verse that includes a period of exponentialexpansion, or inflation. Perhaps, 13 billionyears after the Big Bang, we are once againentering an inflationary period driven bysome scalar condensate.

The two new papers1,2 (the work of Far-don, Kaplan, Nelson and Weiner) present aninteresting argument in which neutrinos arean integral component of the dark energy.They consider the existence of new particles(with masses of about 10�3 electronvolts)that generate the dark energy, and the possi-ble interactions between these particles andthe known particles of the standard model.As far as quarks and charged leptons (such aselectrons) are concerned, there are severeconstraints on the strengths of these inter-actions, called couplings. However, theauthors point out that neutrinos — weaklyinteracting, very-low-mass particles — areexceptional, and cosmologically relevantcouplings are still possible for them.

Indeed, if the dark energy consists ofsome very weakly coupled new species ofparticle,neutrinos offer a better way of prob-ing it directly for a variety of reasons.Because

Cosmology

Neutrino probes of dark energyGia Dvali

Dark energy drives the accelerating expansion of the Universe — butwhat is dark energy? Its influence on the properties of neutrinos mightbe detectable, and could reveal something of its mysterious nature.

The discovery that the rate of expan-sion of the Universe is acceleratinghas created a confusing situation in

cosmology and particle physics. Althoughthe standard cosmological model has beenconfirmed by data from the WMAP spacetelescope and by other telescope surveys ofthe large-scale structure of the Universe,nobody knows why the cosmic expansion isaccelerating. The effect has been attributedto some mysterious gravitational sourcecalled ‘dark energy’, but this name is merelya codeword for something unknown.Theoretical explanations have been postu-lated, some of which should be testable

through precise cosmological measure-ments and gravitational interactions. Butnow Kaplan et al.1, in Physical Review Letters, and Fardon et al.2, in the Journal ofCosmology and Astroparticle Physics, pro-pose that innocuous subatomic particles —neutrinos — might offer a nongravitationalmeans of probing the nature of dark energy.

The accelerating rate of expansion hasbeen inferred directly from surveys of distantsupernovae3,4, but it also fits well with allother existing cosmological data. Super-novae, the cataclysmic explosions of dyingstars, are often used in astronomical surveysas ‘standard candles’,because their brightness

APC

S

S S

SS

S

S

M G1 S

UbcH10

Cdh1 APC

UbcH10

Cdh1 APC

UbcX

Cdh1

S

UbcH10Cyclin A

a cb

Cdh1Cdh1Cdh1

UbUb

Ub UbUb

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Figure 2 A mystery solved. Cyclin A accumulates towards the end of G1 phase, but its destroyer, APC,is still active. How can this happen? Rape and Kirschner1 have provided the answer. They found that,in early G1 phase (a), UbcH10 is busy helping APC to find and add ubiquitin to substrates thatremain from the preceding mitosis. b, Only after most of these have been degraded can UbcH10 addubiquitins to itself, triggering its own destruction. c, The absence of UbcH10 allows cyclin A toaccumulate, whereas other APC substrates can still be degraded through the actions of other Ubcproteins (UbcX). The self-destruction of UbcH10 is an ‘autonomous sensor’ of mitotic completion,and also provides the molecular switch that allows cells to proceed from DNA segregation and celldivision to the new round of DNA duplication.

of this fundamental mechanism1 is animportant addition to our understanding ofthe very basis of cellular multiplication. ■

Jiri Lukas and Jiri Bartek are at the Danish Cancer Society, Institute of Cancer Biology,Strandboulevarden 49, DK-2100 Copenhagen,Denmark.e-mail: lukas@biobase.dk1. Rape, M. & Kirschner, M. W. Nature 432, 588–595 (2004).

2. Murray, A. W. Cell 116, 221–234 (2004).3. Peters, J. M. Mol. Cell 9, 931–943 (2002).

4. Pagano, M., Pepperkok, R., Verde, F., Ansorge, W. & Draetta, G.

EMBO J. 11, 961–971 (1992).

5. Sudakin, V. et al. Mol. Biol. Cell 6, 185–197 (1995).

6. Brandeis, M. & Hunt, T. EMBO J. 15, 5280–5289 (1996).

7. Lukas, C. et al. Nature 401, 815–818 (1999).

8. Sorensen, C. S. et al. Mol. Cell. Biol. 21, 3692–3703 (2001).

9. Hsu, J. Y., Reimann, J. D., Sorensen, C. S., Lukas, J. & Jackson,

P. K. Nature Cell Biol. 4, 358–366 (2002).

10.Pagano, M. & Benmaamar, R. Cancer Cell 4, 251–256 (2003).

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© 2004 Nature Publishing Group

sorting depends on the regulation of clath-rin self-assembly and disassembly; suchpathways can be elucidated by defining the molecular interfaces in the clathrin lattice.

The first structural model4 of the clathrinlattice (at 21 Å resolution) was generated sixyears ago, using electron cryomicrosopy andimage averaging, and revealed that each lat-tice edge comprises leg segments from fourdifferent triskelia. The centre of a triskelionlies at each vertex; the legs extend outwards,spanning two edges and converging beneathanother vertex. Fotin et al.1 have now createda model at much higher resolution (7.9–11 Åresolution) by averaging the images of indi-vidual leg segments, taking advantage oftheir greater symmetry compared with thatof the whole triskelion.

Clathrin has in fact been so well studiedthat only one unexpected — albeit very infor-mative — feature emerges from the newmodel. But the model also provides invalu-able information about how the knownclathrin features fit into the bigger picture ofthe lattice. The familiar features include thefact that the entire linear portion of the tri-skelion leg, from the trimerization domain(TXD) to the terminal domain (TD), isformed by tandemly repeated structuralmotifs called clathrin heavy-chain repeats(CHCRs), previously observed in the heavy-chain X-ray structure5. The link between thefar (distal) leg segment and the TD, pre-viously thought to be flexible6, comprises the eighth CHCR and forms part of a newlydefined ankle segment. The portion of thelight chain that binds to the heavy chain local-izes with the contacts previously identifiedfrom mutational analyses and a molecular-dynamics simulation, and places the centralregions of the light chains with respect to theassembled lattice, confirming that they lie onthe outside and parallel to the heavy chains7.The localization of heavy-chain sequences at

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of their weak interactions, there is still muchabout neutrinos that we don’t know (possi-ble interactions with dark-energy particlesincluded); and because the neutrino mass isso small, it is very sensitive to weak physics.Furthermore, neutrinos do not carry anyconserved quantum numbers, such as elec-tric charge or colour. Most particle inter-actions are allowed or forbidden on the basisof conservation of quantum number (forexample, the total electric charge must be thesame before and after an interaction). Theonly conserved internal quantum numberthat neutrinos might have is the so-calledlepton number (the lepton number of theneutrino is 1, and that of the antineutrino is �1). But there are excellent theoreticalreasons for thinking that the lepton numbermight not be conserved after all (in fact, thismight be the reason for the matter–anti-matter imbalance in the Universe). If this isso, neutrinos are free to mix with the hiddenparticles responsible for the dark energy.

The authors show1,2 that, if the neutrinosdo mix with a hidden sector of dark-energyparticles, the masses of the neutrinos wouldrespond to the finite density of relic neutri-nos in the Universe,changing with the rate ofexpansion of the Universe. In this way, theyhave circumvented the standard argumentagainst ordinary known particles being con-nected with dark energy: although the num-ber density of the particles gets diluted asusual with the expansion, the energy densitydoes not. Some fraction of the energy isstored in the masses of the particles, andsome fraction in the scalar-field potential.The sum of the two can dilute very slowly,even though the number density of neutri-nos dilutes quickly. In such a way, the gas ofneutrinos filling the Universe is promotedinto an undilutable substance,dark energy.

Neutrino masses that change over time inthis way, depending on their environment,have profound phenomenological conse-quences. As Kaplan et al.1 point out, thiswould open up the possibility of probingdark energy through neutrino oscillations— the transformation of one type of neutrinointo another that has now been observedexperimentally7.Neutrino masses are usuallyconsidered to be constants and independentof the density of a surrounding medium.With this condition relaxed,one might expectinteresting deviations from the standard oscil-lation picture,deviations that might shed newlight on existing experimental discrepancies.

The consequences for experiments couldbe significant indeed. If the neutrino masschanges on cosmological time scales, it doesnot affect structure formation in a standardway. Thus, the neutrino mass measured todaymight be larger than the values excluded forconstant-mass neutrinos.From the ever moreprecise data on neutrinos from the Sun,backed up by data from the KamLANDexperiment, which uses neutrinos generated

Cell biology

Clathrin’s Achilles’ ankleFrances M. Brodsky

The protein clathrin forms lattice-like coats on transport vesicles thatbud from cell membranes. High-resolution models of the lattice revealinteractions involved in its disassembly once the vesicles have formed.

Cells are busy places, with membranetraffic moving in all directions —from the cell surface to internal com-

partments and back again, and from onecompartment to another. The transportvehicles are tiny, membrane-bound spherescalled vesicles, which bud off from the mem-brane that encloses a compartment (or thecell itself), and fuse with a target membrane.Cargo is sorted into vesicles by so-called coatproteins, of which one of the best known isclathrin.

Clathrin proteins assemble to form a lattice-like membrane coat, and a strikingnew high-resolution model of this coat isdescribed by Fotin et al.1 on page 573 of thisissue. The model reveals the most detailedpicture so far of clathrin’s contacts in the lattice. On page 649 Fotin et al.2 provide afurther model, that of fragments of anotherprotein, auxilin, bound to the lattice. Fromthis, they suggest how auxilin could disrupt alattice contact to trigger coat disassembly —an essential process for recycling clathrinand delivering cargo to its destination.

Clathrin-coated vesicles serve numerousfunctions in the cell. They internalize nutri-ent receptors and signalling receptors, regu-lating a cell’s sustenance and its stimulationby environmental factors. They also recap-ture membrane at neuronal synapses andsort out proteins in the secretory pathway(reviewed in ref. 3). Clathrin itself has aremarkable three-legged (triskelion) shape,which is formed by three ‘heavy chains’ andthree ‘light chains’ (Fig. 1a). The self-assem-bly of clathrin triskelia into a regular lattice(see Fig. 2 on page 574; ref. 1) provides theorganizing template that allows receptors to be sequestered into vesicles. Meanwhile,‘adaptor’ molecules stimulate lattice forma-tion at membranes and trap receptors in thevesicle coat, concentrating themselves andthe receptors in the lattice. So, receptor

in nuclear reactors, definite predictions for the energy spectrum of solar neutrinos at theEarth can be made.Deviations from these pre-dictions would signify new physics,such as thenew scalar forces in this dark-energy model1,2.With many neutrino experiments currentlyunder way, there is an exciting possibility thatterrestrial particle-physics experiments couldsoon shed light on the physics controlling thegrandest scales of the Universe. ■

Gia Dvali is at the Center for Cosmology and

Particle Physics, Department of Physics, New YorkUniversity, New York, New York 10003, USA.e-mail: dvali@physics.nyu.edu1. Kaplan, D. B., Nelson, A. E. & Weiner, N. Phys. Rev. Lett. 93,

091801 (2004).

2. Fardon, R., Nelson, A. E. & Weiner, N. J. Cosmol. Astropart. Phys.

10(2004)005 (2004).

3. Perlmutter, S. et al. Astrophys. J. 517, 565–586 (1999).

4. Riess, A. G. et al. Astron. J. 116, 1009–1038 (1998).

5. Dvali, G. Sci. Am. 290, no. 2, 68–75 (2004).

6. Ostriker, J. P. & Steinhardt, P. J. Sci. Am. 284, no. 1, 46–53

(2001).

7. Fukuda, Y. et al. Phys. Rev. Lett. 81, 1562–1567 (1998).

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© 2004 Nature Publishing Group