The perception of cytokinin: a story 50 years in the making.

In 1913, Gottlieb Haberlandt found that phloem exudates from various plant species had the ability to stimulate cell division in wounded potato (Solanum tuberosum) tubers (Haberlandt, 1913). These studies implied the existence of a soluble factor(s) that could promote cell division in plant cells. In the 1950s, work primarily by Carlos Miller in Folke Skoog’s laboratory identified cytokinin as a factor that, in concert with auxin, promoted cell division in plant cells (Miller et al., 1955, 1956). This role in cell division has since become one of the defining characteristics of cytokinin and an area of intense research interest, particularly in how it relates to the control of meristem activity. However, cytokinins do more than just regulate cell division. Cytokinins have also been implicated in many plant growth and developmental processes, including organogenesis, leaf senescence, vascular differentiation, sink/source relationships, and nutrient acquisition (Mok and Mok, 1994, 2001; Davies, 2004). Recent decades have seen a flowering of cytokinin research at the molecular level, with key steps in cytokinin biosynthesis, metabolism, and signal transduction having been elucidated. Naturally occurring cytokinins areN-substituted adenine derivatives, and the genes encoding biosynthetic enzymes have been identified in plants, as have genes encoding several important cytokinin metabolic enzymes, including cytokinin oxidase, glucosyltransferase, and xylosyltransferase (Martin et al., 1999a, 1999b, 2001; Mok and Mok, 2001; Kakimoto, 2003a). In addition, as shown in Figure 1, a model for cytokinin perception and signaling has emerged that is similar to bacterial two-component phosphorelays (Kieber, 2001; Hutchison and Kieber, 2002; Sheen, 2002; Heyl and Schmulling, 2003; Kakimoto, 2003b; Grefen and Harter, 2004; Mizuno, 2004; Ferreira and Kieber, 2005). In bacteria, His kinase receptors generally perceive an environmental stimulus, which in turn regulates their autophosphorylation on a His residue (Stock et al., 2000). The phosphate group is in turn transmitted to an Asp residue on a response regulator, thus modulating its function, which is often to act as a transcription factor. There is a more complex version of two-component elements that includes two additional phosphotransfers, which, as in simple two-component systems, occur in sequence His-Asp-His-Asp. It is this phosphorelay mechanism that is found in plant and fungal species, including the cytokinin response pathway (Fig. 1). Although various clues implicated a two-component signaling pathway in cytokinin signaling about 15 years ago, it was not until the turn of the millennium that a cytokinin receptor was definitively identified. Here, we describe how the cytokinin receptor was identified and discuss the implications and future directions enabled by this finding. Readers are referred to other recent reviews for more detailed discussions of the signaling pathway and role of cytokinin in the regulation of plant growth and development (Müller and Sheen, 2007; To and Kieber, 2008; Werner and Schmulling, 2009).