Peptides as signals - Intercellular Communication in Plants - page 37

proliferation. For instance, the phenotypes of clv1 and clv3 null mutants and clv1
clv3 double mutants are nearly identical.
The three CLV genes have been cloned. The CLV3 gene encodes a 96-amino acid
protein that shares no significant sequence similarity to other proteins with known
functions (Fletcher et al. , 1999). It contains a predicted 18-amino acid N-terminal
signal peptide that directs the protein into the secretory pathway. CLV1 encodes a
receptor kinase and, like BRI1 and the PSK receptor, it has an extracellular LRR
domain and an intracellular kinase domain (Clark et al. , 1997). CLV2 is similar
to CLV1 but lacks a cytoplasmic kinase domain. The identification of the CLV
proteins suggests that CLV1 and CLV2 function as the receptors, and CLV3 acts as
the extracellular ligand. CLV1 and CLV2 likely form a heterodimer (Jeong et al. ,
1999; Trotochaud et al. , 1999). Binding of CLV3 with CLV1/CLV2 activates the
receptor, which then recruits additional signaling components to form a 450-kDa
signaling complex, leading to activation of downstream effectors (Trotochaud et al. ,
2000; Clark, 2001).
Studies on expression patterns of the CLV genes have generated important insights
into their functions. CLV3 is expressed predominantly in the L1 and L2 layers at
the apex of the shoot apical meristem. However, CLV1 is predominantly expressed
in the L3 cells, largely beneath the CLV3 expression domain (Fletcher et al. , 1999).
The results indicate that CLV3 acts as a short-distance signal that is secreted from
the L1 and L2 layers and diffused to the inner cell layers where it is perceived by
CLV1/CLV2 to restrict stem cell proliferation.
If the CLV pathway functions to restrict stem cell proliferation, then how is stem
cell homeostasis maintained? Sharma et al. (2003) has proposed a feedback loop
model in which the CLV pathway and a positive, stem-cell-promoting pathway in-
teract to maintain the balance between cell loss and cell division. The homeodomain
transcription factor WUSCHEL (WUS) is a key component of the cell-promoting
pathway. WUS is required for maintaining the stem cell reservoir, and its loss-of-
function mutant is unable to maintain a pool of pluripotent stem cells, resulting in
meristem termination (Laux et al. , 1996; Mayer et al. , 1998). The WUS-mediated
positive pathway acts to promote stem cell proliferation. The resulting enlargement
of the stem cell population leads to increased production of the CLV3 ligand. As a
consequence, it activates the CLV-mediated negative pathway. The enhanced CLV-
signaling then causes reduction in the level of WUS transcription, which in turn
reduces production of CLV3. The resulting reduction in the CLV-mediated nega-
tive pathway then activates the positive pathway. Through this mutual regulation
equilibrium is attained.
The identification of the components in the CLV1 450-kDa complex would lead
to the identification of additional players involved in the CLV pathway. At least
two proteins have been identified from the complex (Trotochaud et al. , 1999). The
first one is the kinase-associated protein phosphatase (KAPP). In contrast to pro-
tein kinases, phosphatases often switch off a response through dephosphorylation.
KAPP likely negatively regulates CLV1 action by dephosphorylating CLV1. Another