Eukaryotes are able to cope with the dynamic variations in their surrounding environment by activating intracellular signal transduction pathways. Transmembrane receptor proteins associated with the plasma membrane (PM) are the primary elements in signaling pathways and therefore perform key functions in organism survival. PM receptors perceive and are activated by extrinsic ligands such as bacterial molecules or intrinsic cellular signals. Once activated, PM receptors auto-phosphorylate and recruit and phosphorylate other proteins, triggering intracellular signal transduction cascades (Zipfel, 2008; Boller and Felix, 2009). Signaling cascades phosphorylate intracellular proteins causing changes in their abundance and activity, and modify the gene expression program of the cell to elicit specific physiological responses (Aker and de Vries, 2008; Tor et al., 2009; Bethani et al., 2010). While receptor ligands, activation manner, and the derivative signaling pathways have been characterized for a number of plant receptors, the mechanisms that govern the functional expression of receptors at their membrane site of action are less understood. In particular, the events that lead to the transport of receptors to the PM and the regulation of these events in response to cellular and environmental cues are largely unknown in plants.

Intracellular transport of proteins involves a network of membranous compartments connected by transport vesicles and other transport structures. Both soluble proteins and proteins containing hydrophobic transmembrane domains rely on the general protein trafficking machinery for delivery via the secretory (also called “anterograde”) pathway to their final destinations. In plants, the endoplasmic reticulum (ER), Golgi complex, and trans-Golgi network (TGN) form the secretory transport conduit. In addition, a large number of organelle-associated proteins and lipids confer compartment identity, perform inter- and intra-compartment transport, and guide the trafficking of protein cargo (Carter et al., 2004; Jurgens, 2004; Dunkley et al., 2006). The transport of proteins within the plant secretory pathway is a dynamic and complex process. In the ER, membrane proteins destined for secretion accumulate in transport vesicles coated with the coat protein complex-II (COPII), which then bud from the ER-exit sites (ERESs). The COPII vesicles capture the mobile Golgi stacks from the cytosol and transfer their contents into the Golgi complex (Brandizzi et al., 2002; Runions et al., 2006; Staehelin and Kang, 2008). The transport factors that guide proteins from the ER to the Golgi return to the ER via coat protein complex-I (COPI)-coated vesicles (Stefano et al., 2006). As proteins progress through the Golgi, they undergo the final maturation steps and are subsequently transferred to the TGN, a sorting station which releases proteins to the PM (Staehelin and Kang, 2008). Targeted fusion of transport vesicles with the PM is facilitated by an octameric complex, the exocyst (Hala et al., 2008; Zhang et al., 2010).

Given its inherent functions, the secretory pathway modulates the spatial and temporal distribution of a large fraction of cellular signaling elements, including receptors, co-receptors, and other associated components. It is generally accepted that plant PM-associated signaling receptors rely on the constitutive, generic secretory transport route to mature and reach destination sites on membranes (Rojo and Denecke, 2008; Cai et al., 2011). Nevertheless, the critical roles of the receptors in the cell along with the diversity in their functional and structural characteristics strongly argue for a high degree of flexibility in their biosynthesis and delivery to the activity sites. In yeast and animals, several factors under the control of the secretion process including the cellular amount of receptor molecules, intracellular compartmentalization, and the steady-state distribution and density of receptors at the PM, were found to govern the signaling specificity, amplitude, and the nature of the physiological output. Moreover, a highly regulated secretion process that guides the secretion of PM receptors was described in humans. This regulated secretion process was found to employ elements of the generic transport machinery but also to recruit additional receptor-specific components. The recruited proteins physically associate with nascent receptors and act as an interface between the receptor and the secretion machinery respond to relevant changes in the cellular environment. For example, events including the presence of ligands and accumulation of secondary messengers such as calcium ions, impact the efficiency of receptor secretion rate, and introduce additional checkpoints for its regulation. These and additional aspects of the PM receptor secretion in eukaryotic systems other than plants, have been described in numerous reviews (Mellman and Nelson, 2008; Cooray et al., 2009; Winckler and Mellman, 2010; Shilo and Schejter, 2011). It is clear that regardless of the receptors’ cellular function, structural characteristics or organism of origin, highly controlled and efficient pathways for the production and transport to the PM is a common requirement.

Whether such a regulated secretory process exists in plants to mediate the transport of PM-associated receptors is still an open question. Nevertheless, evidence accumulated over recent years argues for an important role of secretion in modulating the signaling functions of plant receptors. For instance, the steady-state levels of accumulation at the PM of one of the known tomato ethylene receptors (LeETR4) or of the Arabidopsis flagellin receptor (FLS2), correlated with the strength of their signaling output following activation by ligands. Suppression of LeETR4 expression by RNAi resulted in an early-ripening tomato fruit (Kevany et al., 2008); likewise, reduced FLS2 accumulation at the PM impaired the accumulation of reactive oxygen species (Boutrot et al., 2010; Mersmann et al., 2010). Moreover, quantification of the cellular levels of BRI1, brassinosteroid receptor (Li and Chory, 1997), revealed that BRI1 accumulated at the PM in an organ-dependent manner (Harter and Witthhoft, 2011; van Esse et al., 2011). Furthermore, a number of plant receptor-interacting proteins belonging to various classes have been discovered by recent work and shown to influence the biosynthesis, transport, and functional performance of receptors at the PM.

This article will discuss two aspects of receptor trafficking to the PM: (I) the role of ER and the ER-associated factors in the maturation and quality control of nascent receptors for release into the secretory pathway, and (II) a potential model for the transport of plant receptors out of the ER to the cell surface (Figure 1).

The anterograde transport of proteins is coupled with the process of protein maturation which occurs in the ER. Maturation includes the correct folding and the addition of post-translational modifications to newly synthesized polypeptides (Jurgens, 2004; Staehelin and Kang, 2008). Newly synthesized transmembrane proteins enter the secretory pathway at the ER, following translocation into the ER membrane via the translocon complex (Agarraberes and Dice, 2001; Rapoport, 2007). The ER proteome is enriched in molecular chaperones that promote the correct folding and glycosylation of imported proteins (Molinari and Helenius, 2000; Kleizen and Braakman, 2004). ER chaperones recruit nascent membrane proteins by binding to their exposed ER-retention domains, hydrophobic regions, or glycosylation motifs (Reddy and Corley, 1998; Smith et al., 2011). The recent work describing the role of several plant ER molecular chaperones in receptor maturation or export out of the ER is outlined below (Table 1).

In animals, the coordination between receptor transport and cellular signaling output is achieved through interactions of PM receptors with receptor–accessory proteins (RAPs) located in compartments of the anterograde transport pathway. RAPs regulate receptor accumulation at the cell surface and distribution in active PM microdomains (McLatchie et al., 1998; Petaja-Repo et al., 2000; Bermak et al., 2001; Cooray et al., 2009; Díaz, 2010). Similar mechanisms can be envisioned to exist in plants. So far, several proteins were found to influence receptor signaling, and therefore, have the potential to act like animal RAPs: the reticulon-like proteins RTNLB1 and RTNLB2 and the remorin MtSYREM1. A possible addition to this group is the multi-domain protein KEG. Current evidence for the role of plant RAPs (Table 1) in coordinating receptor transport, PM distribution and function is discussed below.

The direct or indirect interactions discovered thus far between receptors and proteins that are associated with the secretory transport pathway indicate that the biosynthesis and transport of functional receptors is a complex process that requires multiple steps and various activities that function in a step-wise and cooperative manner. In particular, the ER acts as a central hub for the control of biosynthesis and intracellular distribution of signaling-competent receptors. Furthermore, the ER appears to enable the fine-tuning of signal transduction by RAP-mediated modulation of the cellular concentrations and functions of receptors at their activity sites.

Although we have only a superficial understanding of how receptor spatial and temporal distributions are regulated, the work summarized in this review clarifies the importance of a number of accessory proteins and also raises interesting questions. Future research will reveal to what extent accessory proteins are needed and what other mechanisms may exist in plants for regulating receptor functions. Furthermore, it will be critical to uncover the sequence determinants responsible for the regulation of receptors. Ultimately, understanding how intracellular trafficking controls cellular physiological outcomes will allow us to modulate fundamental plant traits such as growth and response to stress.

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.