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6. Franks, N.R., Dornhaus, A., Fitzsimmons, J.P., and Stevens, M. (2003). Speed versus accuracy in collective decision making. Proc. R. Soc. Lond. B 270, 2457–2463. 7. Mettke-Hofmann, C., and Gwinner, E. (2004). Differential assessment of environmental information in a migratory and a non-migratory passerine. Anim. Behav. 68, 1079–1086. 8. Chittka, L., and Osorio, D.C. (2007). Cognitive dimensions of predator responses to imperfect mimicry. PLoS Biol. 5, 2754–2758. 9. Ings, T.C., and Chittka, L. (2008). Speed accuracy tradeoffs and false alarms in bee responses to cryptic predators. Curr. Biol. 18, 1520–1524. 10. Burns, J.G. (2005). Impulsive bees forage better: the advantage of quick, sometimes inaccurate foraging decisions. Anim. Behav. 70, e1–e5. 11. Raine, N.E., Ings, T.C., Dornhaus, A., Saleh, N., and Chittka, L. (2006). Adaptation, genetic drift, pleiotropy, and history in the evolution of bee foraging behavior. Adv. Stud. Behav. 36, 305–354.
12. Nettle, D. (2006). The evolution of personality variation in humans and other animals. Am. Psychol. 61, 622–631. 13. Burns, J.G., and Dyer, A.G. (2008). Diversity of speed-accuracy strategies benefits social insects. Curr. Biol. 18, R953–R954. 14. Peter, C.I., and Johnson, S.D. (2008). Mimics and magnets: the importance of color and ecological facilitation in floral deception. Ecology 89, 1583–1595. 15. Real, L.A. (1981). Uncertainty and pollinatorplant interactions: the foraging behavior of bees and wasps on artificial flowers. Ecology 62, 20–26. 16. Seeley, T.D. (1994). Honey bee foragers as sensory units of their colonies. Behav. Ecol. Sociobiol. 34, 51–62. 17. Waddington, K.D. (2001). Subjective evaluation and choice behavior by nectar- and pollen-collecting bees. In Cognitive Ecology of Pollination, L. Chittka and J.D. Thomson, eds. (Cambridge: Cambridge University Press), pp. 41–60.
Plant Signaling: Brassinosteroids, Immunity and Effectors Are BAK ! Plants use the same set of co-receptors to mediate distinct responses to external signals. Brassinosteroid signaling serves as a test case to unravel the mechanisms of receptor–co-receptor activation and initiation of a specific signaling cascade. Gre´gory Vert Plant growth and development are driven by a complex network of internal signals, including brassinosteroids (BRs), the polyhydroxylated steroid hormones of plants. Over the past decade, genetic and biochemical approaches have provided a wealth of information on BR perception and signaling, but the precise molecular mechanisms driving receptor complex activation and signal transduction to downstream ‘actors’ are still not fully understood [1]. Recent reports have elucidated how BR perception leads to sequential activation of the receptor– co-receptor complex and have identified new BR signaling components acting directly downstream of the receptor. Unlike animal steroid hormones, which are mostly perceived by the nuclear receptor family of transcription factors, BRs bind directly to the extracellular domain of BRI1, a leucine-rich repeat receptor-like kinase (LRR-RLK) that is localized to the plasma membrane [2]. Binding of BRs to pre-existing BRI1 homo-oligomers leads to BRI1 autophosphorylation and to transphosphorylation of the LRR-RLK
BAK1/SERK3 [3–6]. Unexpectedly, BAK1, together with other homologs of the SERK subfamily, was recently shown to regulate cell death and to function in multiple pathogenassociated molecular pattern (PAMP) responses, including responses to flagellin, EF-Tu, bacterial cold-shock protein, and oomycete elicitor INF1, that serve as the first line of defense against pathogens [7–10]. Analogous to its interaction with BRI1, BAK1 was shown to rapidly associate with the LRR-RLK flagellin-binding receptor FLS2 shortly after ligand stimulation [7]. However, BAK1 binds neither BRs nor flagellin [6,7]. Instead, BAK1 appears to act as a general co-receptor of the main ligand-binding receptor, together likely forming a signaling-competent hetero-oligomer. Interestingly, BAK1 has also been shown to promote BRI1 and FLS2 internalization into endosomes [11,12], reminiscent of ligand-induced activation, multimerization and internalization of animal single-pass transmembrane receptors. Therefore, it is unclear whether BAK1’s main function is to activate the ligand-binding receptor, to bridge the receptor with downstream components, or to promote receptor endocytosis.
18. Page, R.E., Scheiner, R., Erber, J., and Amdam, G.V. (2006). The development and evolution of division of labor and foraging specialization in a social insect. Curr. Top. Dev. Biol. 74, 253–285. 19. Mattila, H.R., and Seeley, T.D. (2007). Genetic diversity in honey bee colonies enhances productivity and fitness. Science 317, 362–364. 20. Chittka, L. (2002). Influence of intermittent rewards in learning to handle flowers in bumblebees (Hymenoptera: Apidae: Bombus impatiens). Entomologia Generalis 26, 85–91.
Research Centre for Psychology; School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, UK. E-mail:
[email protected]
DOI: 10.1016/j.cub.2008.09.001
To crack the code of BR receptor complex activation, Wang and colleagues [13] thoroughly dissected, in vitro and in vivo, the sequential mechanisms leading to BRI1 and BAK1 phosphorylation, and how differential receptor activation correlates with signaling. This interesting study revealed that BRI1 acts independently of its co-receptor BAK1 to bind its ligand, to initiate kinase activation and to sustain basal BR signaling and responses, as visualized by the elongation of the hypocotyl (the plant embryonic stem). However, full BR responses arise from the association between activated BRI1 and BAK1 and subsequent transphosphorylation of BAK1’s activation loop residues. Activated BAK1, in turn, transphosphorylates BRI1 in the juxtamembrane and carboxy-terminal domains, leading to enhanced BRI1 kinase activity and BR signaling (Figure 1A). More importantly, the authors provide the first framework for grasping how differential phosphorylation of BAK1 by associated ligand-binding receptor kinases likely explains its participation in different signaling pathways. Notably, BAK1 residue T450 is phosphorylated by BRI1 in vitro and, presumably, in vivo, but mutation of the corresponding residue does not affect the various BAK1-dependent signaling pathways to the same extent. Indeed, phenotypic analysis of plants expressing a T450A non-phosphorylatable BAK1 mutant version revealed that phosphorylation at this BAK1 residue may be important to activate BRI1 and
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Figure 1. BAK1-dependent signaling pathways. (A) Brassinosteroid (BR) perception by BRI1 triggers its autophosphorylation (P) and phosphorylation-dependent release of BKI1 and BSK proteins from the receptor, allowing basal signal transduction by BSKs to downstream factors and association of BRI1 with BAK1. Transphosphorylation of BAK1 leads, in turn, to full activation of BRI1 by further BRI1 phosphorylation and promotes enhanced BR responses. (B) P. syringae injects into the cell the AvrPto and AvrPtoB effectors, which bind to BAK1 and prevent its flagellin-dependent association with FLS2 and other pattern recognition receptors (PRRs), leading to PAMP-triggered immunity (PTI) suppression. Other BAK1-dependent pathways, such as BR signaling and cell death, are also affected.
especially FLS2 but may not be required for cell death regulation. A comparative analysis of BAK1 in vivo phosphorylation sites in BR versus flagellin-treated plants is needed to shed additional light on the phosphorylated residues leading to differential BAK1 activation by BRI1 and FLS2 and, in turn, on the role of BAK1 in the subsequent activation of different LRR-RLKs. Does BAK1 have other roles besides just activating the ligand-binding receptor? How about the role of BAK1 in receptor endocytosis? One would expect to observe ligand-dependent receptor endocytosis considering that
BAK1 associates with the main receptor upon ligand binding. While this scenario fits well with the data obtained for FLS2 [7,11], a recent study elegantly demonstrated that BRI1 is endocytosed in a BR-independent manner [14]. Further conclusions on the role of BAK1 in endocytosis of BRI1 will await a detailed analysis of BRI1 internalization in bak1 mutant plants. As part of the receptor complex, can activated BAK1 signal to downstream components? Probably not in the case of BR signaling, considering that overexpression of BAK1 is unable to suppress strong bri1 alleles [3,4], although
overexpression of an ‘activated’ form of BAK1 containing phosphomimetic mutations at sites phosphorylated by BRI1 may be more conclusive. Moreover, no overlap between responses induced by BR and flagellin exist. Finally, no BAK1-interacting proteins acting downstream of BRI1 and FLS2 receptors in the corresponding signaling pathways have been reported. This supports the notion that BAK1 solely functions in receptor activation, leaving the signaling to the ligand-binding receptor. Despite extensive genetic screens looking for BR-related mutants, a major gap remains between BR perception and downstream events in the signaling cascade, such as the inactivation of the BIN2 GSK3 kinase [1]. Why is this so? From these past unsuccessful attempts we can deduce that the relevant genes are either functionally redundant or that the loss of their functions results in lethality. Searches for BRI1-interacting proteins have identified several potential actors, although their in vivo role in BR signaling is not well understood. Only the BRI1-kinase interactor BKI1 has been shown to limit BRI1 and BAK1 interaction to prevent receptor activation in the absence of BRs [15]. In a recent report, Tang and colleagues [16] identified the BSK receptor-like cytosolic kinases as new BRI1 substrates. BSK1 interacts in vivo with plasma-membrane-localized BRI1, with BRs decreasing their association (Figure 1A). Loss- and gain-of-function genetic analyses of some BSK family members suggest that they are positive regulators of BR signaling, acting upstream of BIN2. A model emerges in which BSKs might be released from the receptor upon phosphorylation by BRI1 to transduce the signal to downstream components. Again, BAK1 turns out to be unable to interact with BSKs, further supporting the hypothesis that BR signaling to downstream actors initiates from BRI1. Whether BIN2, whose plasma membrane localization has already been documented [17], is a substrate of BSK kinase activity remains an open question in this ‘grail quest’ for the missing downstream factors. While the puzzle of the core BR signaling cascade rapidly assembles, its interaction with other pathways has slowly come to light. Not only do BR
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and defense signaling pathways share BAK1 [3,4,7,9], but recent work from Shan and colleagues [18] provides evidence that some bacterial effectors strike back at PAMP-triggered immunity (PTI) by targeting BAK1. Effectors are usually injected into plant cells by successful bacteria upon infection to evade recognition or to suppress the subsequent signaling steps. Previous work revealed that AvrPto and AvrPtoB, two unrelated effectors from Pseudomonas syringae DC3000, target early steps in various PAMP signaling pathways, apparently upstream of a MAP kinase cascade important for PTI [19]. Shan et al. [18] now report that both effectors bind in vivo with high affinity to BAK1, and prevent its ligand-dependent interaction with FLS2. Moreover, artificial overexpression of AvrPto and AvrPtoB in transgenic Arabidopsis leads to BR-related dwarfism, likely resulting from BAK1’s inability to associate with BRI1 (Figure 1B). This interesting observation will have to be confirmed using natural levels of bacterial-delivered effectors to evaluate if BR signaling is actually downregulated upon infection with P. syringae. If this scenario holds true, could inhibition of BR signaling be thought of as collateral damage in this war between plants and their pathogens? Do bacterial effectors intentionally target BR-mediated growth or pathogen resistance, which BRs have been linked to [20]? The rationale for disabling a general co-receptor and interfering with several BAK1-dependent pathways is not clear yet. One can imagine that bacteria manipulate several PTI responses, including BR signaling and cell death, to increase pathogenicity and to team up with other pathogens to overwhelm plant defenses. Future studies should provide a new basis for understanding how BR signaling is interconnected with other pathways, and why different signaling cascades co-opted the same co-receptor to mediate complex and specific responses. References 1. Vert, G., Nemhauser, J.L., Geldner, N., Hong, F., and Chory, J. (2005). Molecular mechanisms of steroid hormone signaling in plants. Annu. Rev. Cell Dev. Biol. 21, 177–201. 2. Kinoshita, T., Cano-Delgado, A., Seto, H., Hiranuma, S., Fujioka, S., Yoshida, S., and Chory, J. (2005). Binding of brassinosteroids to the extracellular domain of plant receptor kinase BRI1. Nature 433, 167–171.
3. Li, J., Wen, J., Lease, K.A., Doke, J.T., Tax, F.E., and Walker, J.C. (2002). BAK1, an Arabidopsis LRR receptor-like protein kinase, interacts with BRI1 and modulates brassinosteroid signaling. Cell 110, 213–222. 4. Nam, K.H., and Li, J. (2002). BRI1/BAK1, a receptor kinase pair mediating brassinosteroid signaling. Cell 110, 203–212. 5. Wang, X., Goshe, M.B., Soderblom, E.J., Phinney, B.S., Kuchar, J.A., Li, J., Asami, T., Yoshida, S., Huber, S.C., and Clouse, S.D. (2005). Identification and functional analysis of in vivo phosphorylation sites of the Arabidopsis BRASSINOSTEROID-INSENSITIVE1 receptor kinase. Plant Cell 17, 1685–1703. 6. Wang, X., Li, X., Meisenhelder, J., Hunter, T., Yoshida, S., Asami, T., and Chory, J. (2005). Autoregulation and homodimerization are involved in the activation of the plant steroid receptor BRI1. Dev. Cell 8, 855–865. 7. Chinchilla, D., Zipfel, C., Robatzek, S., Kemmerling, B., Nurnberger, T., Jones, J.D., Felix, G., and Boller, T. (2007). A flagellininduced complex of the receptor FLS2 and BAK1 initiates plant defence. Nature 448, 497–500. 8. He, K., Gou, X., Yuan, T., Lin, H., Asami, T., Yoshida, S., Russell, S.D., and Li, J. (2007). BAK1 and BKK1 regulate brassinosteroiddependent growth and brassinosteroidindependent cell-death pathways. Curr. Biol. 17, 1109–1115. 9. Heese, A., Hann, D.R., Gimenez-Ibanez, S., Jones, A.M., He, K., Li, J., Schroeder, J.I., Peck, S.C., and Rathjen, J.P. (2007). The receptor-like kinase SERK3/BAK1 is a central regulator of innate immunity in plants. Proc. Natl. Acad. Sci. USA 104, 12217–12222. 10. Kemmerling, B., Schwedt, A., Rodriguez, P., Mazzotta, S., Frank, M., Qamar, S.A., Mengiste, T., Betsuyaku, S., Parker, J.E., Mussig, C., et al. (2007). The BRI1-associated kinase 1, BAK1, has a brassinolideindependent role in plant cell-death control. Curr. Biol. 17, 1116–1122. 11. Robatzek, S., Chinchilla, D., and Boller, T. (2006). Ligand-induced endocytosis of the pattern recognition receptor FLS2 in Arabidopsis. Genes Dev. 20, 537–542. 12. Russinova, E., Borst, J.W., Kwaaitaal, M., Cano-Delgado, A., Yin, Y., Chory, J., and de Vries, S.C. (2004). Heterodimerization and endocytosis of Arabidopsis brassinosteroid
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receptors BRI1 and AtSERK3 (BAK1). Plant Cell 16, 3216–3229. Wang, X., Kota, U., He, K., Blackburn, K., Li, J., Goshe, M.B., Huber, S.C., and Clouse, S.D. (2008). Sequential transphosphorylation of the BRI1/BAK1 receptor kinase complex impacts early events in brassinosteroid signaling. Dev. Cell 15, 220–235. Geldner, N., Hyman, D.L., Wang, X., Schumacher, K., and Chory, J. (2007). Endosomal signaling of plant steroid receptor kinase BRI1. Genes Dev. 21, 1598–1602. Wang, X., and Chory, J. (2006). Brassinosteroids regulate dissociation of BKI1, a negative regulator of BRI1 signaling, from the plasma membrane. Science 313, 1118–1122. Tang, W., Kim, T.W., Oses-Prieto, J.A., Sun, Y., Deng, Z., Zhu, S., Wang, R., Burlingame, A.L., and Wang, Z.Y. (2008). BSKs mediate signal transduction from the receptor kinase BRI1 in Arabidopsis. Science 321, 557–560. Vert, G., and Chory, J. (2006). Downstream nuclear events in brassinosteroid signalling. Nature 441, 96–100. Shan, L., He, P., Li, J., Heese, A., Peck, S.C., Nurnberger, T., Martin, G.B., and Sheen, J. (2008). Bacterial effectors target the common signaling partner BAK1 to disrupt multiple MAMP receptor-signaling complexes and impede plant immunity. Cell Host Microbe 4, 17–27. He, P., Shan, L., Lin, N.C., Martin, G.B., Kemmerling, B., Nurnberger, T., and Sheen, J. (2006). Specific bacterial suppressors of MAMP signaling upstream of MAPKKK in Arabidopsis innate immunity. Cell 125, 563–575. Nakashita, H., Yasuda, M., Nitta, T., Asami, T., Fujioka, S., Arai, Y., Sekimata, K., Takatsuto, S., Yamaguchi, I., and Yoshida, S. (2003). Brassinosteroid functions in a broad range of disease resistance in tobacco and rice. Plant J. 33, 887–898.
Biochimie et Physiologie Mole´culaire des Plantes, CNRS UMR 5004, Institut de Biologie Inte´grative des Plantes, 2 place viala 34060 Montpellier, France. E-mail:
[email protected]
DOI: 10.1016/j.cub.2008.09.006
Cognitive Neuroscience: Searching for the Bottleneck in the Brain People simply cannot do two things at once, as shown by research on the so-called psychological refractory period. A new neuroimaging study has now localized the response-selection bottleneck underlying the psychological refractory period to a frontoparietal network. Charles Spence The notion that dual-task performance in humans is fundamentally constrained by some kind of internal bottleneck goes back more than half a century to the pioneering early work of Kenneth Craik, Alan Welford, and Margaret Vince [1,2]. In recent years, most research on this topic has been conducted within the framework of the
‘psychological refractory period’ — the interference (or delay) in responding to the second of two stimuli that is observed when they are presented close together in time. Hal Pashler and his colleagues [3,4] have published an impressive number of behavioral studies on the psychological refractory period showing, time-and-again, that people simply cannot perform two tasks at once, no matter how much
