CLAVATA and BR Signaling Pathways

As with the Drosophila Toll signaling pathway, there are some similarities between elements of the BR and CLAVATA signaling pathways in Arabidopsis. Mutations in three CLAVATA loci, CLV1, CLV2, and CLV3, result in similar phenotypes of enlarged shoot meristems. CLV1 is a LRR-RLK (Clark et al., 1997; Figure 4B), and CLV2 is a LRR receptor–like protein (Jeong et al., 1999; Figure 4A), whereas CLV3 is a small secreted peptide (Fletcher et al., 1999). Both genetic (Fletcher et al., 1999) and biochemical (Trotochaud et al., 1999) studies indicate that CLV1 forms a heterodimeric receptor complex with CLV2. Further biochemical (Trotochaud et al., 2000) and controlled expression analysis of CLV3 (Brand et al., 2000) has shown that CLV3 interacts as a multimeric ligand with a CLV1 complex, and that CLV1 kinase activity is required for CLV3 binding (Trotochaud et al., 2000). The CLV1 complex exists in two distinct states, a smaller disulphide-linked presumed heterodimer of CLV1 and CLV2, and a larger complex that includes the heterodimer, a kinase-associated protein phosphatase (KAPP) and a rho GTPase–related protein (Trotochaud et al., 1999). It is postulated that the ?-related protein may provide the signaling mechanism to downstream targets, whereas KAPP acts as a negative regulator (Williams et al., 1997; Stone et al., 1998). The fact that the CLV1/CLV2 heterodimer is linked via disulfide bonds suggests a role for cysteines at either end of the LRRs (Figure 4). CLV signaling directly or indirectly downregulates the expression of Wuschel (WUS), which negatively regulates the differentiation of meristematic stem cells. WUS is required for expression of CLV3. Thus, downregulation of WUS leads to a decrease of CLV3 levels, which in turn reduces the CLV1/CLV2 activation that leads to upregulation of WUS, ensuring a delicate balance in the control of meristem differentiation (Clark, 2001).

Relevant to BR signaling, KAPP has been observed to interact with a number of LRR-RLKs, including BRI1 (Schumacher and Chory, 2000). It will be intriguing, therefore, to learn whether overexpression of KAPP or a KAPP homolog leads to a bri1-like phenotype and upregulation of genes in BR biosynthesis. Initial results from such a study indicated that only a clavata phenotype was observed when overexpressing KAPP (Williams et al., 1997). Furthermore, it remains to be determined whether BRI1 is capable of forming heterodimeric complexes with other LRR receptor–like proteins or LRR-RLKs in analogy with CLV1/CLV2. In respect to global control of steroid metabolism, it will be also interesting to learn whether BRI1 can interact with SBPs or some steroid-conjugated signaling factors showing analogy to the SONIC/HEDGEHOG proteins that play crucial roles in the regulation of cell differentiation pathways in mammals (Porter et al., 1996; Lewis et al., 2001).

• Other Sections?
  • INTRODUCTION
  • BL SIGNALING MECHANISM, CONCLUSIONS AND PROSPECTS
  • References

BL SIGNALING MECHANISM, CONCLUSIONS AND PROSPECTS

According to the speculative models discussed above, BR perception may imply the formation of BRI1-associated receptor complexes (Figure 5). The BRI1 complex might interact either directly with BL or with a secreted and processed sterol binding/carrier protein that could undergo BRS-mediated proteolytic processing. Nonetheless, it is currently unknown whether BRI1 is capable of forming a heterodimeric receptor complex with other LRR-RLKs or LRR receptor–like proteins. A recent meeting report on the existence of a BRI1-interacting kinase, which is a LRR-RLK and forms a RLK heterodimer with BRI1, supports model A in Figure 5 (Eckartdt et al., 2001). BL is known to promote autophosphorylation and activation of BRI1, triggering downstream responses, which may be modulated by BRI1 binding an inhibitory KAPP-like protein phosphatase. A phosphorylation cascade, including, for example, MAPK(K/K) kinases, may ensure signal amplification leading to the activation of transcription factors that control activation (e.g., XET) or repression (e.g., BR biosynthesis) of BR-responsive genes. Alternatively, BRI1 may directly phosphorylate transcription factors and other signaling components (e.g., TRIP) modulating perse cellular responses. BIN2 appears to play a role as negative regulator acting downstream of BRI1 in this signaling pathway.

Further genetic screens for mutations that suppress or enhance the above-described mutations and/or confer resistance to the BR biosynthesis inhibitor brassinozole are expected to unravel new elements of BR signaling. In addition, biochemical and protein interaction studies will help in the identification of signaling partners of BRI1 and BIN2 kinases. Also expected to be derived from further studies of BL signaling is a major input toward gaining detailed insight into the regulation of nongenomic steroid signaling, which may facilitate the understanding of similar pathways in other organisms. In particular, it is hoped that the study of plant steroid hormone signaling pathways, based on the use of comparative genome analysis, will uncover the conservation of some signaling functions that also play a pivotal role in nongenomic control of sterol homeostasis and steroid hormone metabolism in mammals. As a practical goal, further exploration of BR signaling and its interaction with other hormonal and developmental pathways is predicted to provide new strategies for the regulation of growth and improvement in yield of important crops.

Acknowledgments

Categories: General Health Topics