Q&A: How do plants respond to cytokinins and what is their importance?
© Osugi and Sakakibara. 2015
Published: 27 November 2015
Cytokinins comprise a family of signaling molecules essential for regulating the growth and development of plants, acting both locally and at a distance. Although much is known about their biosynthesis and transport, important open questions remain.
What are cytokinins?
What are the physiological functions of cytokinins?
Cytokinins were originally defined as chemicals that induce cell proliferation and trigger callus differentiation to shoot when applied with auxins, but now it is known that cytokinins play a key role in many aspects of plant growth and development , including embryogenesis, maintenance of root and shoot meristems, and vascular development. They also modulate root elongation, lateral root number, nodule formation, and apical dominance in response to environmental stimuli. Thus, cytokinins are important signaling molecules for regulating growth and development throughout the life of the plant.
What is the physiological concentration of cytokinins?
The recent development of mass spectrometry technology has enabled us to quantify the concentration of phytohormones and their conjugates at the organ level. Based on such analyses, for which the values are generally 0.1 to 10 pmol g−1 fresh weight, it may be estimated that the in vivo concentration of cytokinins is at the nanomolar level, and that concentration may vary between different organs and growth conditions. Notably, if cytokinins are unevenly distributed in the organs at either the tissue or cellular level, their local concentration could be higher or lower. The affinity (apparent K D) of cytokinin receptors to their ligands is around 1–40 nM , which would make the estimated nanomolar concentration of cytokinins physiologically relevant.
How do plants sense cytokinins?
AHKs are membrane-localized cytokinin receptors which consist of three domains: CHASE, histidine kinase, and receiver [2, 3, 6]. The binding of cytokinins to the AHK CHASE domain triggers autophosphorylation of a His residue in its histidine kinase domain, and the phosphoryl group is internally transferred to an Asp residue in its receiver domain. Recent studies suggest that the cytokinin receptors are localized in both the plasma membrane and the endoplasmic reticulum [7, 8], but it is still unclear whether both are functional or not.
AHPs mediate the transfer of a phosphoryl group from cytosolic AHKs to nuclear-localized type-B ARRs [3, 9]. Type-B ARRs possess a receiver domain for the phosphoryl group, a DNA-binding domain (GARP domain), and a glutamine-rich domain for transcriptional activation . Transcriptional activation by ARRs is repressed in the non-phosphorylated state . When phosphorylated, type-B ARRs can bind target DNA sequences and activate transcription of target genes.
Since each member of the AHK, AHP and type-B ARR gene families is functionally redundant, clear phenotypic differences are not observed in their single mutants. However, responsiveness to cytokinins is severely reduced and growth phenotypes could be observed in multiple mutants within each gene family [11–13], indicating that the cytokinin TCS plays a central role in cytokinin responses in plants.
How does the TCS modulate its signaling flux?
In order to finely regulate cytokinin signaling, multiple feedback loops of the cytokinin TCS are employed to ensure the appropriate signaling flux (Fig. 2). In addition to the 11 type-B ARRs, the Arabidopsis genome has ten type-A ARR genes (ARR3–ARR9, ARR15–ARR17) , and some of them are direct targets of type-B ARRs. Like type-B ARRs, type-A ARRs possess a receiver domain and receive a phosphoryl group from AHPs, but they lack a DNA-binding domain. Thus, type-A ARRs can potentially inhibit the cytokinin signaling flux by competing with type-B ARRs for phosphate transfer .
Differential regulation of posttranslational stability of type-B ARRs is involved in the modulation of the TCS signaling flux. Cytokinins promote degradation of ARR2 via the 26S proteasome  while they stabilize ARR1 by preventing degradation by 26S proteasome . On the other hand, KISS ME DEADLY proteins (KMDs), a family of F-box proteins, are involved in degrading ARR1, ARR2 and ARR12, but the detailed mechanisms have yet to be discovered .
It has also been reported that an AHP homologue, AHP6, which lacks the conserved histidine for phosphoryl group transfer, physically interacts with AHKs but does not receive a phosphate, suggesting that AHP6 inhibits cytokinin response through competition with canonical AHPs. Cytokinins repress AHP6 expression , which suggests that the promotion of cytokinin signaling flux is in part mediated by the down-regulation of AHP6. It was reported that cell-specific expression of AHP6 serves spatial specification of cytokinin signaling [19, 20]. In addition, cytokinins induce the expression of a cytokinin receptor gene, AHK4/WOL1/CRE1, which might lead to increased sensitivity to cytokinins . It has been proposed that occurrence of these feedback loops in an organ- or a cell-specific manner is important for regulation of cytokinin signaling flux, as described later.
How are cytokinins produced and metabolized in plants?
For the catabolism of cytokinins, cytokinin oxidase/dehydrogenase (CKX) irreversibly degrades cytokinins by cleaving the unsaturated isoprenoid side chain, which results in the formation of adenine and the corresponding aldehyde . Glycosylation of cytokinins also plays an important role in modulating cytokinin activity: N-glucosylation of the N7 and N9 positions of the adenine moiety and O-glucosylation of the zeatin side chain are catalyzed by UGT76C1 and C2, and 85A1, respectively, in Arabidopsis [3, 30]. Because of their biological stability, the glucosides are the most abundant components of cytokinin derivatives, making up 80 % or more of total cytokinin-related compounds in plants (Fig. 1b). These glucosides are thought to be sequestered in the vacuole. In addition, ribosidation and ribotidation by purine salvage pathway enzymes contribute to the cycling of cytokinins, through reverting active forms back to inactive precursors (Fig. 3). Thus, homeostasis of cytokinin activity is maintained by multiple metabolic systems.
Where are cytokinins produced in plants?
How important are locally produced cytokinins for plant development?
In order to maintain shoot apical meristem, it is necessary to channel the cytokinin signal towards the organizing center . In shoot apical meristem, active cytokinins are produced in the L1 layer by LOG4 and in the central zone by LOG7 [35, 36]. The organizing center and rib meristem are responsive to cytokinins via AHK4/WOL1/CRE1 (Fig. 5a) . Endogenous cytokinins activate cytokinin signaling only in the organizing center but not in the rib meristem, although exogenously applied cytokinins activate both of these tissues (Fig. 5a) . This indicates that the longitudinal diffusion of cytokinins to adjacent regions and local action in the restricted cells are important for proper meristem function.
The importance of local activation of cytokinins is also shown in the early stage of root vascular development. In root tip vasculature, which consists of procambium, protoxylem, metaxylem and phloem (Fig. 5b), cytokinin-activating LOG3 and LOG4 are specifically expressed in protoxylem cells, while cytokinin-perceiving AHK4/WOL1/CRE1 is expressed in the procambium [19, 20]. Analysis using marker genes for cytokinin response revealed that procambium cells adjacent to protoxylem respond to cytokinins more strongly than distant procambium cells [19, 20], indicating that local activation of cytokinins in protoxylem specifies cytokinin perception cells in procambium. Since cytokinins inhibit procambium-to-protoxylem differentiation, this regulation may be necessary for proper positioning of those cells during vascular development.
Root morphogenesis is abnormal in the log3 log4 log7 triple mutant, possibly due to reduced levels of active cytokinin . Expression of LOG3 under a xylem precursor cell-specific promoter rescues this phenotype. However, ectopic expression of LOG3 in the phloem, through which cytokinins are systemically transported, does not. Therefore, it is suggested that the locally synthesized cytokinins are necessary for root morphogenesis.
How important are distantly translocated cytokinins for plant growth and development?
Movement of cytokinins between organs has been shown by tracer experiments using isotope-labeled cytokinins [31, 37–39] and detection of cytokinins in vascular saps also supports translocation of cytokinins . In general, long-distance signals are translocated through xylem and phloem, two major conduits for material transfer in plant vasculature. Intriguingly, these studies show that cytokinin species are unevenly distributed: tZ-type cytokinins are more abundant than iP-type in xylem sap and vice versa in phloem sap  (Fig. 4). These studies imply that iP-type and tZ-type cytokinins are directionally translocated and transmit different biological messages between organs.
Grafting experiments support the importance of cytokinins as long-distance signals. The Arabidopsis ipt1 ipt3 ipt5 ipt7 quadruple mutant shows severely reduced cytokinin content and shoot and root growth-deficient phenotypes . Reciprocal grafting between the quadruple mutant and wild type rescued the growth-deficient phenotypes in shoot and root with accompanying recovery of cytokinin content , indicating a role of root-borne cytokinins in shoot and vice versa.
Grafting experiments also show the importance of root-borne tZ for normal shoot growth. In the cyp735a1 cyp735a2 double mutant, tZ-type cytokinin content is severely reduced without affecting total cytokinin quantity, and shoot growth is retarded . When the shoot of the double mutant is grafted onto wild-type stock, the shoot phenotype is complemented with accompanying recovery of tZ-type cytokinin content, suggesting that side chain modulation of cytokinins has a specialized role in their long-distance translocation for shoot growth regulation.
As for the role of shoot-borne cytokinin in roots, impairing phloem transport destabilizes root vascular development with an accompanying reduction of basipetal cytokinin translocation in Arabidopsis . Thus, shoot-borne cytokinins, via phloem, could participate in normal development of root vasculature in coordination with locally produced cytokinins.
In Lotus japonicas, root nodule number is reduced in the Ljipt3 cytokinin biosynthesis gene mutant , as well as in a Ljipt3 knockdown transgenic line . Grafting between Ljipt3 shoot and wild-type root stock represses nodulation, while reverse grafting does not . This suggests that shoot-derived cytokinins function as a repression signal of nodulation. It is notable that cytokinins synthesized in the root are not significantly involved in regulation of nodule number, although the mechanism through which the origin of cytokinins is determined remains to be elucidated.
So far, studies have shown that both xylem and phloem sap contain vast amounts of cytokinin ribonucleosides , suggesting that cytokinin ribonucleosides are translocated through the vasculature. It is believed that the cytokinin ribonucleosides are converted to their ribonucleotides followed by activation via LOG where they function.
How is long-distance translocation of cytokinins regulated?
An elaborate translocation system is necessary for the regulation of organ-to-organ communication via cytokinins. Recent studies identified ATP-binding cassette transporter subfamily G14 (ABCG14) as a key gene for appropriate root-to-shoot cytokinin translocation [39, 43]. In abcg14, tZ-type cytokinin contents are greatly reduced in xylem sap, and the dwarf phenotype of abcg14 is rescued in grafted plants between abcg14 shoot and wild-type root stock , indicating that ABCG14 is an essential gene for root-to-shoot translocation of cytokinins. Since the biochemical properties of ABCG14 have not been well characterized, the substrate of ABCG14 has not been identified. In addition to ABCG14, purine permease 1 and 2 (PUP1 and PUP2) and equilibrate nucleoside transporter (ENT) have been shown in in vitro studies to be involved in transport of cytokinins [44, 45]. However, their functions in planta, especially in long-distance translocation of cytokinins, are still poorly characterized.
What determines the site of cytokinin action?
Spatial regulation of LOG expression is one of the determining factors that specify the functional sites of cytokinins, and expression of each LOG family gene is regulated in a site-specific manner [25, 32]. Recently, a mechanism for this site-specific expression of LOG genes has been reported in flower development in Arabidopsis . In a mutant of APETALA1 (AP1), a MADS-BOX transcriptional factor, abnormal floral organs are observed. AP1 directly represses LOG1 expression, and possibly in sepals where their expression overlaps. LOG1 repression, under control of the AP1 promoter, partially rescued the ap1 phenotype, indicating that sepal-specific LOG1 repression is required for normal flower development. In addition, expression of a LOG homolog is directly activated by KNOTTED1 (KN1) in maize . It is thought that KN1 might provide site-specific regulation of the LOG homolog’s coordination with certain BEL1-LIKE HOMEOBOX (BLH) gene products, which interact with KN1 to bind DNA.
Recent studies have also revealed the importance of cytokinin oxidase/dehydrogenase (CKX) function as a metabolic attenuator of local cytokinin action. As well as LOG, the expression of each CKX family gene is regulated in a site-specific manner . Loss-of-function mutants of specific CKX genes in rice (OsCKX2) and Arabidopsis (CKX3 and CKX5), which are expressed in reproductive meristem, cause increased cytokinin levels, leading to larger meristem size and an increase in reproductive organ number [48, 49], clearly showing that the CKXs fine-tune active cytokinin levels at the expression site. CKX3 expression in the organizing center and CKX5 broadly in the meristematic domain  may be particularly important for ensuring the site-specific cytokinin response (Fig. 5a). It is also intriguing that Arabidopsis AP1, which negatively regulates LOG1 expression, positively regulates CKX3 in the sepal . This regulation is important for development of a determinate floral meristem.
Another candidate to control functionality of cytokinins is the family of AHK proteins. AHK promoter:reporter gene analyses revealed that the cytokinin receptors are expressed in various tissues in the plant, but that AHK3 is preferentially expressed in aerial organs, such as rosette leaves, AHK4/WOL1/CRE1 is expressed in root, and AHK2 is expressed in both . Interestingly, it is reported that their affinities to ligands are different: AHK2 and AHK4/WOL1/CRE1 bind with similar affinity to tZ as well as iP, while AHK3 has less affinity to iP than to tZ [4, 50]. Thus, it is expected that tZ plays a major role as a cytokinin in shoots. This supports previous work with cyp735a1 cyp735a2 identifying a specialized function of tZ in shoot development .
Some other components of the cytokinin TCS also contribute to determining the sites of action of cytokinins. Cytokinins induce expression of WUSCHEL (WUS), a transcriptional factor expressed in the organizing center of the shoot apical meristem. WUS directly binds to the promoters of ARR5, ARR6, ARR7, and ARR15, and represses their expression (Fig. 5) . This regulation establishes a local spatial domain for the organization of a stem cell niche in the shoot apex. (Fig. 5) .
What interactions occur between cytokinins and other phytohormones?
Signaling systems of phytohormones build a network and mutually regulate signaling, transport, and metabolic systems. Interplay between cytokinins and auxin is one of the best-characterized cases of hormone–hormone interaction. Recent studies shed light on the importance of cytokinin–auxin interaction for auxin traffic and specification of cytokinin action sites in root vascular development. Cytokinin signaling in the procambium up-regulates expression of PINs, a family of auxin efflux carriers, and promotes their distribution in the plasma membrane from anticlinal to periclinal . The bisymmetric distribution of PINs channels basipetally translocates auxin to protoxylem via the procambium. The auxin is perceived in the protoxylem and induces LONESOME HIGHWAY (LHW) and TARGET OF MONOPTEROS5 (TMO5). They directly induce LOG3 and LOG4, which activate cytokinins, and AHP6, which inhibits cytokinin responses in the protoxylem [19, 20]. Thus, the auxin-induced LOG3 and LOG4 in protoxylem provides cytokinins to adjacent procambium for proper root vascular development while the induced AHP6 inhibits cytokinin response (Fig. 5b) [19, 20]. Consequently, the procambial cytokinin response regulates PIN expression and distribution.
What is the important question for the future?
Cytokinins positively regulate agriculturally important traits such as grain size and biomass  but they also promote unfavorable phenotypes such as inhibition of root elongation. Therefore, spatio-temporal regulation of cytokinins is required for appropriate function in specific organs. In this article, we have discussed the spatial regulation of cytokinin biosynthesis and the role of these hormones in signaling. In order to better utilize cytokinin action to enhance beneficial traits of crops, a deeper understanding of their temporal regulation will be necessary.
The authors are supported by MEXT NC-CARP and JST CREST.
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- Sakakibara H. Cytokinins: activity, biosynthesis and translocation. Annu Rev Plant Biol. 2006;57:431–49.View ArticlePubMedGoogle Scholar
- Yamada H, Suzuki T, Terada K, Takei K, Ishikawa K, Miwa K, et al. The Arabidopsis AHK4 histidine kinase is a cytokinin-binding receptor that transduces cytokinin signals across the membrane. Plant Cell Physiol. 2001;42:1017–23.View ArticlePubMedGoogle Scholar
- Kieber JJ, Schaller GE. Cytokinins. In The Arabidopsis book. American Society of Plant Biologists; 2014:12.Google Scholar
- Lomin SN, Krivosheev DM, Steklov MY, Arkhipov DV, Osolodkin DI, Schmülling T, et al. Plant membrane assays with cytokinin receptors underpin the unique role of free cytokinin bases as biologically active ligands. J Exp Bot. 2015. doi:10.1093/jxb/eru522.PubMed CentralPubMedGoogle Scholar
- Kakimoto T. CKI1, a histidine kinase homolog implicated in cytokinin signal transduction. Science. 1996;274:982–5.View ArticlePubMedGoogle Scholar
- Inoue T, Higuchi M, Hashimoto Y, Seki M, Kobayashi M, Kato T, et al. Identification of CRE1 as a cytokinin receptor from Arabidopsis. Nature. 2001;409:1060–3.View ArticlePubMedGoogle Scholar
- Lomin SN, Yonekura-Sakakibara K, Romanov GA, Sakakibara H. Ligand-binding properties and subcellular localization of maize cytokinin receptors. J Exp Bot. 2011;62:5149–59.PubMed CentralView ArticlePubMedGoogle Scholar
- Wulfetange K, Lomin SN, Romanov GA, Stolz A, Heyl A, Schmülling T. The cytokinin receptors of Arabidopsis are located mainly to the endoplasmic reticulum. Plant Physiol. 2011;156:1808–18.PubMed CentralView ArticlePubMedGoogle Scholar
- Hwang I, Sheen J. Two-component circuitry in Arabidopsis cytokinin signal transduction. Nature. 2001;413:383–9.View ArticlePubMedGoogle Scholar
- Sakai H, Honma T, Aoyama T, Sato S, Kato T, Tabata S, et al. ARR1, a transcription factor for genes immediately responsive to cytokinins. Science. 2001;294:1519–21.View ArticlePubMedGoogle Scholar
- Higuchi M, Pischke MS, Mähönen AP, Miyawaki K, Hashimoto Y, Seki M, et al. In planta functions of the Arabidopsis cytokinin receptor family. Proc Natl Acad Sci U S A. 2004;101:8821–6.PubMed CentralView ArticlePubMedGoogle Scholar
- Mason MG, Mathews DE, Argyros DA, Maxwell BB, Kieber JJ, Alonso JM, et al. Multiple type-B response regulators mediate cytokinin signal transduction in Arabidopsis. Plant Cell. 2005;17:3007–18.PubMed CentralView ArticlePubMedGoogle Scholar
- Hutchison CE, Li J, Argueso C, Gonzalez M, Lee E, Lewis MW, et al. The Arabidopsis histidine phosphotransfer proteins are redundant positive regulators of cytokinin signaling. Plant Cell. 2006;18:3073–87.PubMed CentralView ArticlePubMedGoogle Scholar
- Kiba T, Yamada H, Sato S, Kato T, Tabata S, Yamashino T, et al. The type-A response regulator, ARR15, acts as a negative regulator in the cytokinin-mediated signal transduction in Arabidopsis thaliana. Plant Cell Physiol. 2003;44:868–74.View ArticlePubMedGoogle Scholar
- Kim K, Ryu H, Cho Y-H, Scacchi E, Sabatini S, Hwang I. Cytokinin-facilitated proteolysis of Arabidopsis response regulator 2 attenuates signaling output in two-component circuitry. Plant J. 2012;69:934–45.View ArticlePubMedGoogle Scholar
- Kurepa J, Li Y, Smalle JA. Cytokinin signaling stabilizes the response activator ARR1. Plant J. 2014;78:157–68.View ArticlePubMedGoogle Scholar
- Kim HJ, Chiang Y-H, Kieber JJ, Schaller GE. scfKMD controls cytokinin signaling by regulating the degradation of type-B response regulators. Proc Natl Acad Sci U S A. 2013;110:10028–33.PubMed CentralView ArticlePubMedGoogle Scholar
- Mähönen AP, Bishopp A, Higuchi M, Nieminen KM, Kinoshita K, Törmäkangas K, et al. Cytokinin signaling and its inhibitor AHP6 regulate cell fate during vascular development. Science. 2006;311:94–8.View ArticlePubMedGoogle Scholar
- Ohashi-Ito K, Saegusa M, Iwamoto K, Oda Y, Katayama H, Kojima M, et al. A bHLH complex activates vascular cell division via cytokinin action in root apical meristem. Curr Biol. 2014;24:2053–8.View ArticlePubMedGoogle Scholar
- De Rybel B, Adibi M, Breda AS, Wendrich JR, Smit ME, Novák O, et al. Integration of growth and patterning during vascular tissue formation in Arabidopsis. Science. 2014;345:1255215.View ArticlePubMedGoogle Scholar
- Kiba T, Aoki K, Sakakibara H, Mizuno T. Arabidopsis response regulator, ARR22, ectopic expression of which results in phenotypes similar to the wol cytokinin-receptor mutant. Plant Cell Physiol. 2004;45:1063–77.View ArticlePubMedGoogle Scholar
- Kakimoto T. Identification of plant cytokinin biosynthetic enzymes as dimethylallyl diphosphate: ATP/ADP isopentenyltransferases. Plant Cell Physiol. 2001;42:677–85.View ArticlePubMedGoogle Scholar
- Takei K, Sakakibara H, Sugiyama T. Identification of genes encoding adenylate isopentenyltransferase, a cytokinin biosynthesis enzyme, in Arabidopsis thaliana. J Biol Chem. 2001;276:26405–10.View ArticlePubMedGoogle Scholar
- Takei K, Yamaya T, Sakakibara H. Arabidopsis CYP735A1 and CYP735A2 encode cytokinin hydroxylases that catalyze the biosynthesis of trans-zeatin. J Biol Chem. 2004;279:41866–72.View ArticlePubMedGoogle Scholar
- Kurakawa T, Ueda N, Maekawa M, Kobayashi K, Kojima M, Nagato Y, et al. Direct control of shoot meristem activity by a cytokinin-activating enzyme. Nature. 2007;445:652–5.View ArticlePubMedGoogle Scholar
- Tokunaga H, Kojima M, Kuroha T, Ishida T, Sugimoto K, Kiba T, et al. Arabidopsis lonely guy (LOG) multiple mutants reveal a central role of the LOG-dependent pathway in cytokinin activation. Plant J. 2012;69:355–65.View ArticlePubMedGoogle Scholar
- Takei K, Ueda N, Aoki K, Kuromori T, Hirayama T, Shinozaki K, et al. AtIPT3 is a key determinant of nitrate-dependent cytokinin biosynthesis in Arabidopsis. Plant Cell Physiol. 2004;45:1053–62.View ArticlePubMedGoogle Scholar
- Kamada-Nobusada T, Makita N, Kojima M, Sakakibara H. Nitrogen-dependent regulation of de novo cytokinin biosynthesis in rice: the role of glutamine metabolism as an additional signal. Plant Cell Physiol. 2013;127:1881–93.View ArticleGoogle Scholar
- Miyawaki K, Matsumoto-Kitano M, Kakimoto T. Expression of cytokinin biosynthetic isopentenyltransferase genes in Arabidopsis: tissue specificity and regulation by auxin, cytokinin, and nitrate. Plant J. 2004;37:128–38.View ArticlePubMedGoogle Scholar
- Wang J, Ma XM, Kojima M, Sakakibara H, Hou BK. N-glucosyltransferase UGT76C2 is involved in cytokinin homeostasis and cytokinin response in Arabidopsis thaliana. Plant Cell Physiol. 2011;52:2200–1.View ArticlePubMedGoogle Scholar
- Kiba T, Takei K, Kojima M, Sakakibara H. Side-chain modification of cytokinins controls shoot growth in Arabidopsis. Dev Cell. 2013;27:452–61.View ArticlePubMedGoogle Scholar
- Kuroha T, Tokunaga H, Kojima M, Ueda N, Ishida T, Nagawa S, et al. Functional analyses of lonely guy cytokinin-activating enzymes reveal the importance of the direct activation pathway in Arabidopsis. Plant Cell. 2009;21:3152–69.PubMed CentralView ArticlePubMedGoogle Scholar
- Werner T, Motyka V, Laucou V, Smets R, Van Onckelen H, Schmülling T. Cytokinin-deficient transgenic Arabidopsis plants show multiple developmental alterations indicating opposite functions of cytokinins in the regulation of shoot and root meristem activity. Plant Cell. 2003;15:2532–50.PubMed CentralView ArticlePubMedGoogle Scholar
- Leibfried A, To JP, Busch W, Stehling S, Kehle A, Demar M, et al. WUSCHEL controls meristem function by direct regulation of cytokinin-inducible response regulators. Nature. 2005;438:1172–5.View ArticlePubMedGoogle Scholar
- Yadav RK, Girke T, Pasala S, Xie M, Reddy GV. Gene expression map of the Arabidopsis shoot apical meristem stem cell niche. Proc Natl Acad Sci U S A. 2009;106:4941–6.PubMed CentralView ArticlePubMedGoogle Scholar
- Chickarmane VS, Gordon SP, Tarr PT, Heisler MG, Meyerowitz EM. Cytokinin signaling as a positional cue for patterning the apical–basal axis of the growing Arabidopsis shoot meristem. Proc Natl Acad Sci U S A. 2012;109:4002–7.PubMed CentralView ArticlePubMedGoogle Scholar
- Bishopp A, Lehesranta S, Vatén A, Help H, El-Showk S, Scheres B, et al. Phloem-transported cytokinin regulates polar auxin transport and maintains vascular pattern in the root meristem. Curr Biol. 2011;21:927–32.View ArticlePubMedGoogle Scholar
- Sasaki T, Suzaki T, Soyano T, Kojima M, Sakakibara H, Kawaguchi M. Shoot-derived cytokinins systemically regulate root nodulation. Nat Commun. 2014;5:4983.View ArticlePubMedGoogle Scholar
- Zhang K, Novak O, Wei Z, Gou M, Zhang X, Yu Y, et al. Arabidopsis ABCG14 protein controls the acropetal translocation of root-synthesized cytokinins. Nat Commun. 2014;5:3274.PubMedGoogle Scholar
- Hirose N, Takei K, Kuroha T, Kamada-Nobusada T, Hayashi H, Sakakibara H. Regulation of cytokinin biosynthesis, compartmentalization and translocation. J Exp Bot. 2008;59:75–83.View ArticlePubMedGoogle Scholar
- Matsumoto-Kitano M, Kusumoto T, Tarkowski P, Kinoshita-Tsujimura K, Václavíková K, Miyawaki K, et al. Cytokinins are central regulators of cambial activity. Proc Natl Acad Sci U S A. 2008;105:20027–31.PubMed CentralView ArticlePubMedGoogle Scholar
- Chen Y, Chen W, Li X, Jiang H, Wu P, Xia K, et al. Knockdown of LjIPT3 influences nodule development in Lotus japonicus. Plant Cell Physiol. 2013;55:183–93.View ArticlePubMedGoogle Scholar
- Ko D, Kang J, Kiba T, Park J, Kojima M, Do J, et al. Arabidopsis ABCG14 is essential for the root-to-shoot translocation of cytokinin. Proc Natl Acad Sci U S A. 2014;111:7150–5.PubMed CentralView ArticlePubMedGoogle Scholar
- Burkle L, Cedzich A, Dopke C, Stransky H, Okumoto S, Gillissen B, et al. Transport of cytokinins mediated by purine transporters of the PUP family expressed in phloem, hydathodes, and pollen of Arabidopsis. Plant J. 2003;34:13–26.View ArticlePubMedGoogle Scholar
- Hirose N, Makita N, Yamaya T, Sakakibara H. Functional characterization and expression analysis of a gene, OsENT2, encoding an equilibrative nucleoside transporter in Oryza sativa suggest a function in cytokinin transport. Plant Physiol. 2005;138:196–206.PubMed CentralView ArticlePubMedGoogle Scholar
- Han Y, Zhang C, Yang H, Jiao Y. Cytokinin pathway mediates APETALA1 function in the establishment of determinate floral meristems in Arabidopsis. Proc Natl Acad Sci U S A. 2014;111:6840–5.PubMed CentralView ArticlePubMedGoogle Scholar
- Bolduc N, Yilmaz A, Mejia-Guerra MK, Morohashi K, O’Connor D, Grotewold E, et al. Unraveling the KNOTTED1 regulatory network in maize meristems. Genes Dev. 2012;26:1685–90.PubMed CentralView ArticlePubMedGoogle Scholar
- Ashikari M, Sakakibara H, Lin S, Yamamoto T, Takashi T, Nishimura A, et al. Cytokinin oxidase regulates rice grain production. Science. 2005;309:741–5.View ArticlePubMedGoogle Scholar
- Bartrina I, Otto E, Strnad M, Werner T, Schmülling T. Cytokinin regulates the activity of reproductive meristems, flower organ size, ovule formation, and thus seed yield in Arabidopsis thaliana. Plant Cell. 2011;23:69–80.PubMed CentralView ArticlePubMedGoogle Scholar
- Stolz A, Riefler M, Lomin SN, Achazi K, Romanov GA, Schmülling T. The specificity of cytokinin signalling in Arabidopsis thaliana is mediated by differing ligand affinities and expression profiles of the receptors. Plant J. 2011;67:157–68.View ArticlePubMedGoogle Scholar
- Gordon SP, Chickarmane VS, Ohno C, Meyerowitz EM. Multiple feedback loops through cytokinin signaling control stem cell number within the Arabidopsis shoot meristem. Proc Natl Acad Sci U S A. 2009;106:16529–34.PubMed CentralView ArticlePubMedGoogle Scholar
- Bishopp A, Help H, El-Showk S, Weijers D, Scheres B, Friml J, et al. A mutually inhibitory interaction between auxin and cytokinin specifies vascular pattern in roots. Curr Biol. 2011;21:917–26.View ArticlePubMedGoogle Scholar
- Sowerby J, Boswell JT, Lankester P, Salter JW, de C Sowerby J, Sowerby JE. English botany, or coloured figures of British plants, vol. 3. London: R Hardwicke; 1864.Google Scholar