© 2005 Nature Publishing Group

NATURE|Vol 437|13 October 2005 NEWS & VIEWS

965

Mayer and colleagues1 further clarify themechanisms by which CaMKII targets Erp1for destruction, building on three previousfindings concerning a protein called Polo-likekinase 1 (Plk1). This protein choreographsseveral steps in meiosis and mitosis — thebasic cell-division cycle that produces mostcells in the body6. First, Plk1 is required forAPC/CCdc20 activation at the release frommeta-II arrest7. Second, Erp1 is identified as anovel APC/CCdc20 inhibitor that is required formeta-II arrest, and it can be phosphorylated byPlk1 and thereby targeted for degradation8.Third, Plk1 contains a motif called the Polo-box domain (PBD) that can bind to a specificpeptide ‘docking’ sequence in another protein,but only once the peptide has been phospho-rylated by a ‘priming kinase’. This suggests amechanism whereby the priming kinase phos-phorylates the PBD-docking motif in Plk1substrates, allowing Plk1 to bind to the sub-strate and phosphorylate it a second time6,9.

Mayer and colleagues1 demonstrate thatCaMKII functions as a priming kinase for

What controls senescence and lifespan? Asthey describe in Ecology Letters, Mencuccini etal.1 have tackled this question for trees, whichmay live for many centuries and grow to morethan 100 metres in height. With increasing ageand size, growth tends to slow and a tree ismore likely to die. One explanation for this isthat reduced growth results from tissue andcell senescence, which is under direct geneticor age-related control. Another is the physio-logical burdens, such as the demands on waterand nutrient supply, that are associated withincreasing height and girth. Mencuccini andcolleagues’ results add experimental supportfor this second view.

The term senescence encompasses a collec-tion of changes that are associated with ageing.Such changes are triggered by altered geneexpression, and include a progressive loss ofphysiological functions, a decrease of fertilityand a greater vulnerability to disease or dam-age. It has long been believed that senescenceis an inevitable consequence of ageing in allplants and animals. Evidence from diverse disciplines has challenged this assumption foranimals2, however, and there are indicationsthat it may also not apply to trees.

First, there is a difference between cellular,tissue or organ senescence and whole-treesenescence. The former process is fairly well

PLANT PHYSIOLOGY

A big issue for trees Josep Peñuelas

The age of a tree and its size tend to increase together. Disentangling theeffects of these two factors on tree vitality is no easy task, but furtherevidence adds to the view that it is size that matters.

Erp1 — allowing it then to be recognized andphosphorylated by Plk1. The second phospho-rylation of Erp1 targets it for degradation,releasing APC/CCdc20 from inhibition. This thentriggers the exit from meta-II and resumptionof the cell cycle. So the calcium increase afterfertilization sets in motion a precisely regulatedsystem of protein degradation that eventuallyreleases meta-II arrest (Fig. 1). The same pathway probably functions in eggs of othervertebrates. This model explains why Erp1 isnot attacked by Plk1 until fertilization, eventhough Plk1 is active during meta-II arrest.

A close relative of Erp1, called Emi1 (earlymitotic inhibitor 1), is also found in frog eggsand can also inhibit APC/CCdc20 (ref. 10).Although Emi1 was initially thought to beessential for meta-II arrest in the same way asErp1 (ref. 11), this possibility was excluded byits absence during meta-II arrest12. WhetherErp1 is involved in the mitotic cell cycles in theearly embryo is not known, but it is plausiblethat Erp1 inhibits APC/CCdc20 in the egg andearly embryo, and that Emi1 takes over thisrole later in development. Jackson and col-leagues10 propose that Emi1 inhibits theAPC/CCdc20 complex by binding to the Cdc20protein, and it is possible that Erp1 acts in asimilar manner.

Although the studies of Mayer and colleagues1,8 and of Liu and Maller2 have unravelled the mechanism by which meta-IIarrest is relieved following fertilization, itremains unclear how arrest occurs in the firstplace. More than 30 years ago, Masui andMarkert identified cytostatic factor (CSF), acytoplasmic activity responsible for frog meta-II arrest3. Further studies established that CSF

Plk1

RELEASE

Resumecell cycle

Ca2+

CaMKII

P

�

Erp1

APC/CCdc20

ARREST

Finishdivision�Meta-II Meta-II

Erp1

Erp1

APC/CCdc20

P P

Erp1 PP

Fertilization

�

Figure 1 | Releasing the brakes. Frog eggsawaiting fertilization are arrested at the cell-division stage called metaphase of meiosis II(meta-II), owing to the inhibition of theAPC/CCdc20 protein complex. This complex actson certain inhibitors of the next stage in the cellcycle (anaphase), targeting them for degradation.The inhibition of APC/CCdc20 requires Erp1.Upon fertilization, the resulting Ca2+ riseactivates calmodulin-dependent protein kinase II(CaMKII). Mayer and colleagues1 show thatCaMKII phosphorylates Erp1 (circled P), therebycreating a docking site for Polo-like kinase 1(Plk1). The recruited Plk1 phosphorylates Erp1again, thereby targeting it for destruction. As a result, APC/CCdc20 is no longer inhibited, and anaphase inhibitors such as mitotic cyclins and securin are targeted for degradation,leading to the release of meta-II arrest. Thus,CaMKII acts as a novel priming kinase for Erp1 phosphorylation by Plk1, which links the fertilization signal to resumption of the cell cycle. Red crosses indicate steps in thepathway that do not occur.

activity includes a signalling pathway thatinvolves the Mos, MAPK and Rsk proteins(reviewed in refs 3, 13). Although another pro-posed initiator of meta-II arrest is the spindlecheckpoint pathway13, it seems that Mad2, acore component of this pathway, may not beessential for CSF activity2. But if Erp1 can itselfinhibit APC/CCdc20, why is the Mos–MAPK–Rsk pathway required for meta-II arrest? Presumably, Erp1 can cooperate with Mos–MAPK–Rsk to prevent Cdc20 from activatingAPC/CCdc20. If so, CSF may consist of bothErp1 and Mos–MAPK–Rsk. This questionbears further investigation: Erp1 may turn outto be key to the arrest of the cell cycle while theegg awaits fertilization, as well as to its sub-sequent resumption after sperm entry. ■

Takeo Kishimoto is in the Laboratory of Cell andDevelopmental Biology, Graduate School ofBioscience, Tokyo Institute of Technology,Nagatsuta, Midoriku, Yokohama 226-8501,Japan.e-mail: tkishimo@bio.titech.ac.jp

1. Rauh, N. R., Schmidt, A., Bormann, J., Nigg, E. A. & Mayer, T. U. Nature 437, 1048–1052 (2005).

2. Liu, J. & Maller, J. L. Curr. Biol. 15, 1458–1468 (2005).3. Masui, Y. Nature Rev. Mol. Cell Biol. 1, 228–232 (2000). 4. Peters, J. M. Mol. Cell 9, 931–943 (2002).5. Lorca, T. et al. Nature 366, 270–273 (1993).6. Barr, F. A., Sillje, H. H. W. & Nigg, E. A. Nature Rev. Mol. Cell

Biol. 5, 429–440 (2004).7. Descombes, P. & Nigg, E. A. EMBO J. 17, 1328–1335 (1998).8. Schmidt, A. et al. Genes Dev. 19, 502–513 (2005).9. Elia, A. E. H. et al. Cell 115, 83–95 (2003).10. Reimann, J. D. R. et al. Cell 105, 645–655 (2001).11. Reimann, J. D. R. & Jackson, P. K. Nature 416, 850–854

(2002).12. Ohsumi, K., Koyanagi, A., Yamamoto, T. M., Gotoh, T. &

Kishimoto, T. Proc. Natl Acad. Sci. USA 101, 12531–12536(2004).

13. Tunquist, B. J. & Maller, J. L. Genes Dev. 17, 683–710 (2003).

13.10 News & Views 957 MH 7/10/05 5:30 PM Page 965

Nature Publishing Group© 2005

© 2005 Nature Publishing Group

NEWS & VIEWS NATURE|Vol 437|13 October 2005

966

known: for example, leaf senescence occurs asa process of programmed cell death3, and isage-dependent and induced by environmentalcues such as extremes in temperature, lightintensity and duration, or moisture4. But thereis little evidence of changes in gene expressionin ageing trees5, and therefore of geneticallycontrolled mechanisms to explain the reducedgrowth of mature specimens.

Second, the reproductive period of trees canextend over centuries. Their reproductive out-put, instead of declining, increases with age(and therefore size) and the number of poten-tial reproductive buds.

Third, woody plants such as the famousCabernet Sauvignon grapevines have beenpropagated for more than 800 years by serialgrafting6, and aspen clones can apparentlyreplicate indefinitely. So it seems that at leastsome cell lines inside the meristems — thegrowing points from which new cells form —retain the juvenile ability to contribute to newgrowth even in ageing stock.

Finally, slow-growing non-clonal trees canlive for millennia, and apparently still be ingood shape. Such trees tend to inhabit extreme

environments. For example, bristlecone pinesatop the arid mountains in the western United States are more than 4,000 years old(Fig. 1). Trees on the vertical surfaces of cliffslikewise endure harsh conditions, grow onlyslowly and may live for more than 1,000 years7.Slow growth minimizes maintenance andrepair costs, while maximizing durability and strength.

With this as background, Mencuccini et al.1

carried out an experimental test of the pres-ence or absence of senescence-related changesin trees. Their study involved four tree speciesrepresenting different evolutionary groups(gymnosperms and angiosperms), and withdifferent water-transport characteristics (ring-porous, diffusive-porous and tracheid-bear-ing), leaf ecology (evergreen and deciduous)and intensity of management practices(unmanaged and intensively managed). Foreach species, they measured growth, togetherwith the gas-exchange and biochemical prop-erties of leaves, in trees of different ages (1–269years old) and sizes (2–42 metres in height) inthe field. They repeated the measurements onspecimens — now of equally small size — that

had been propagated, by grafting or by directrooting, from the same trees.

Growth, net photosynthetic rates and leafnitrogen concentrations declined in the fieldwith size and age, but there were no suchdeclines in the corresponding propagatedplants. Mencuccini and colleagues conclude,therefore, that size, not meristematic cellularsenescence, accounts for the reduced growthrates in older, taller trees.

As the authors themselves point out, how-ever, it is possible that factors or conditionselsewhere in the tree may still trigger senes-cence in the meristem. These system-level signals could have disappeared in the smallgrafted plants, with the meristems reverting toa more juvenile condition. To check this possi-bility, the same measurements need to be con-ducted on stocks of different sizes. Such workhas in fact been done on Japanese cedars8, inwhich it was found that grafted shoots in theupper crowns of tall cedars showed a similarlypoor performance to intact shoots in thosecrowns. These results provide a further indica-tion that extrinsic factors mediated by size, notirreversible intrinsic changes in the meristems,drive the decline in photosynthetic rates inlarger trees.

Given these observations, we might wonderwhether, if trees remain short, they will remainvigorous. Bonsais can live for hundreds ofyears: do they never senesce, and do they livelonger than their big brothers? And do theshort trees characteristic of Mediterranean climates live longer than tall trees in moisttemperate regions? It still seems unlikely thatsize alone determines tree vigour.

The way forward lies in combining researchin plant physiological ecology and molecularbiology, carried out on both trees and grafts.With more cross-talk between these disci-plines, the aim will be to identify possible bio-chemical and genetic indicators of senescencein meristematic and non-meristematic tissues,and to relate those findings to constraintsimposed by the tree as a whole. The outcomewill be of more than academic value, and ofkeen interest, for example, to those involved inforest conservation and timber production. ■

Josep Peñuelas is at the Consejo Superior deInvestigaciones Científicas (CSIC-CEAB) and theCenter for Ecological Research and ForestryApplications (CREAF), Universitat Autònoma deBarcelona, 08193 Bellaterra, Catalonia, Spain. e-mail: josep.penuelas@uab.es

1. Mencuccini, M. et al. Ecol. Lett. doi:10.1111/j.1461-0248.2005.00819.x (2005).

2. Helfand, S. L. & Inouye, S. Nature Rev. Genet. 3, 149–153(2002).

3. Yoshida, S. Curr. Opin. Plant Biol. 6, 79–84 (2003).4. Munné-Bosch, S. & Peñuelas, J. Ann. Bot. 92, 385–391

(2003).5. Diego, L. B. et al. J. Exp. Bot. 55, 1597–1599 (2004).6. Noodén, L. D. & Thompson, J. E. in Handbook of the Biology

of Aging, 2nd edn (eds Finch, C. E. & Schneider, E. L.)105–127 (Van Nostrand, New York, 1985).

7. Larson, D. W. et al. Nature 398, 382–383 (1999).8. Matsuzaki, J., Norisada, M., Kodaira, J., Suzuki, M.

& Tange, T. Trees 19, 198–203 (2005).

Figure 1 | Lonesome pine. This example of an ancient bristlecone pine stands in the Great BasinNational Park, Nevada.

D. M

UEN

CH

/CO

RBIS

13.10 News & Views 957 MH 7/10/05 5:30 PM Page 966

Nature Publishing Group© 2005