Calcium at the Crossroads of Signaling.docx

1、Calcium at the Crossroads of SignalingThe Plant Cell, S401S417, Supplement 2002, www.plantcell.org 2002 American Society of Plant BiologistsCalcium at the Crossroads of SignalingDale Sanders,a,1 Jrme Pelloux,a Colin Brownlee,b and Jeffrey F. Harper ca Biologyb MarineDepartment, University of York, Y

2、ork YO10 5YW, United KingdomBiological Association, The Laboratory, Citadel Hill, Plymouth PL1 2PB, United Kingdomc Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037INTRODUCTIONCalcium Signals: A Central Paradigm inStimulusResponse CouplingCells must respond to an

3、 array of environmental and devel-opmental cues. The signaling networks that have evolved togenerate appropriate cellular responses are varied and arenormally composed of elements that include a sequence ofreceptors, nonprotein messengers, enzymes and transcrip-tion factors. Receptors are normally h

4、ighly specific for thephysiological stimulus, and therefore are disparate in theiridentities. Likewise enzymes and transcription factors tendtoward specificity, and this fact is reflected in abundance atthe genome level. The Arabidopsis genome, for example,potentially encodes in the region of 1000 p

5、rotein kinases,300 protein phosphatases, and 1500 transcription factors.By contrast, nonprotein messengers are relatively few. Theyinclude cyclic nucleotides (Newton et al., 1999), hydrogenions (Guern et al., 1991), active oxygen species (VanBreusegem et al., 2001), lipids (Ng and Hetherington, 2001

6、;Nurnberger and Scheel, 2001; Munne-Bosch and Alegre,2002), and, above all, calcium.Changes in cytosolic free calcium (Ca 2 c) are apparentduring the transduction of a very wide variety of abiotic andbiotic signals. The spectrum of stimuli that evokes rapidchanges in Ca2 c has been cataloged in a nu

7、mber of re-cent reviews (Sanders et al., 1999; Knight, 2000; Anil andRao, 2001; Knight and Knight, 2001; Rudd and Franklin-Tong, 2001). Abiotic stimuli include lightwith red, blue,and UV/B irradiation each acting via different receptors andleading to distinct developmental responses (Shacklock etal.

8、, 1992; Baum et al., 1999; Frohnmeyer et al., 1999), lowand high temperature, touch, hyperosmotic stress, and oxi-dative stress. Biotic stimuli include the hormones abscissicacid (ABA) and gibberellin, fungal elicitors, and nodulation(Nod) factors.1 To whom correspondence should be addressed. E-mail

9、 ds10york.ac.uk; fax 44-1904-434317.Article, publication date, and citation information can be found atwww.plantcell.org/cgi/doi/10.1105/tpc.002899.The Specificity QuestionAn all-pervading question during the last decade of calciumsignaling research has revolved around the issue of specificity(McAin

10、sh and Hetherington, 1998). How can a simple non-protein messenger be involved in so many signal transduc-tion pathways and yet still convey stimulus specificity within avariety of pathways? Ostensibly there are a number reason-able nonexclusive answers to this question. First, the Ca 2signal itself

11、 might be a necessary but insufficient trigger forthe response, with effective signal transduction occurringonly should another signal change in parallel. Second, speci-ficity might be encoded by the spatial properties of the Ca 2signal, either because the signal is compartmentally localized(for exa

12、mple, to the nucleus, rather than the cytosol) or be-cause the source of the Ca2 signal (from outside the cell orfrom intracellular stores) can selectively trigger response ele-ments. Third, the dynamic properties of the Ca 2 signal mightdetermine the efficacy with which the response is elicited.Fou

13、rth, of course, the appropriate response elements mustbe present in the particular cell type in which the Ca 2 signalarises. Since Ca2 signaling was last reviewed in this journal(Sanders et al., 1999), remarkable advances have been madein addressing this central problem of specificity, in manycases

14、thanks to the insights provided by genetic approaches.Thus, while alluding briefly to the earlier literature, the presentreview will focus on developments in our understanding thathave occurred over the past four years.ELEMENTS ENCODING CALCIUM SIGNALSCalcium signals are generated through the openin

15、g of ionchannels that allow the downhill flow of Ca 2 from a com-partment in which the ion is present at relatively high elec-trochemical potential (either outside the cell, or from anintracellular store) to one in which Ca 2 is at lower potential.There has, in the past, been a tendency to refer to

16、suchchannels as “Ca2 channels,” although we prefer the term“Ca2 -permeable channels” because this reflects the likelyimportance of nonselective cation channels in generatingplant Ca2 signals. Maintenance of low Ca2 electrochemicalactivity in the Ca2 -responsive compartment is achieved byS402The Plan

17、t Cellthe ATP- or proton motive forcedriven removal of Ca 2 onpumps or carriers (transporters), respectively. As shown inFigure 1, the interplay between influx through channels andefflux from pumps and carriers will determine the form of aCa2 spike that is potentially specific to relevant decoders.F

18、igure 2 shows the location of channels, pumps, and carri-ers involved in Ca2 transport for a generalized Arabidopsiscell, as the basis for the discussion below.Calcium-Permeable Ion ChannelsThe importance of the cellular location of ion channels in de-termining stimulus specificity is emphasized by

19、a study ofCa2 -mediated stomatal closure in tobacco (Wood et al.,2000). Removal of extracellular Ca 2 with the chelator EGTAor blockage of entry with a number of ion channel blockerssuggested that low temperatureinduced closure involvesprimarily entry of Ca2 across the plasma membrane, whileintracel

20、lular mobilization appears to dominate if stomatalclosure is initiated with ABA or mechanical stimulation.Calcium-permeable channels have been investigatedwith electrophysiological, biochemical, and molecular ap-proaches, and these are now beginning to yield comple-mentary insights into the nature a

21、nd control of channels thatunderlie the generation of Ca2 signals.cium-permeable channels that are activated by membranedepolarization (reviewed by White, 2000). It has been specu-lated that this form of voltage gating might endow suchchannels with a pivotal role at an early stage in signal trans-du

22、ction (Ward et al., 1995). Thus, perception of a range ofstimuli results in membrane depolarization, possibly as a re-sult of the activation of anion channels, and the resultantopening of depolarization-activated Ca 2 -permeable chan-nels could lead to elevation of Ca 2 c.While depolarization-activa

23、tion of Ca 2 -permeable chan-nels is a recurring theme in a number of biological systems,recent simultaneous and independent studies have followedpioneering work by Gelli et al. (1997) and Gelli and Blumwald(1997) on tomato cell suspensions, reporting the presencein plant plasma membranes of Ca 2 -p

24、ermeable channelsthat are activated by membrane hyperpolarization. Suchchannels have a high selectivity for Ca 2 over K and Cl(Gelli and Blumwald, 1997; Hamilton et al., 2000; Vry andDavies, 2000). It has been known for some time that inguard cells, membrane hyperpolarization is directly asso-ciated

25、 with the elevation of Ca 2 c that follows ABA appli-cation (Grabov and Blatt, 1998). The observation thathyperpolarization-activated Ca2 -permeable channels in theplasma membrane of guard cells are opened by ABA evenin excised membrane patches implies a very close physicalcoupling between the chann

26、els and the sites of ABA per-ception (Hamilton et al., 2000). Channel opening might alsobe subject to negative feedback control to prevent exces-Plasma Membranesive Ca2entry, since activity decreases around ten-foldElectrophysiological studies during the past decade haverevealed the presence in plan

27、t plasma membranes of cal-Figure 1. Decoding Calcium Signals Leads to a Specific Responseat the Cellular Level.Various feedback mechanisms from the calcium sensor (or “de-coder”) are possible. These could include the regulation of calciumspikes via the control of calcium permeable channel gating (e.

28、g.,through EF binding hands, or via Ca2 /CaM binding) or via control ofpump activity.over the range of Ca2 c from 0.2 to 2 M. In root hairs,channel activity is present at the tips of growing cells, butnot detectable in subapical regions or at the tips of maturecells (Vry and Davies, 2000), an observ

29、ation consistentwith the notion that these channels play a pivotal role in thegeneration of the tip-to-base Ca 2 gradient that is essentialfor maintaining polarization in tip-growing systems (includ-ing pollen tubes and rhizoid cells). Intriguingly, the root hairchannels are, in contrast to their co

30、unterparts in guard cells,activated by elevation of Ca2 c, suggesting that they mightplay a self-sustaining role in maintaining the tip-to-baseCa2 gradient. Hyperpolarization-activated Ca 2 -permeablechannels have also been reported in the growing root apexof Arabidopsis roots, but not in other more

31、 mature cells(Kiegle et al., 2000a), possibly suggesting a role for thesechannels in cell division and elongation.ABA-induced stomatal closure involves the production ofreactive oxygen species, notably hydrogen peroxide (Pei etal., 2000; Zhang et al., 2001), and hyperpolarization-acti-vated Ca2 -permeable channels play a critical role in thisreponse. In Arabidopsis guard cells, hydrogen peroxidestimulates hyperpolarization-activated Ca2 -permeable chan-nels, and thereby an increase in Ca 2 c (Pei et al., 2000).This process requires cytosolic NAD(P)H, sugge