Review articleMaster and servant: Regulation of auxin transporters by FKBPs and cyclophilins
Introduction
Numerous developmental processes in multicellular organisms rely on the establishment of tissue polarities [1]. Spatial developmental information in plants is conveyed in part through the directional distribution of the essential hormone, auxin [2]. Auxin accumulation and its directional distribution among neighboring cells, referred to as polar auxin transport, represent the core of the ability of auxin to elicit differential effects on plant growth and development [1]. In this manner, polar auxin transport is a primary mechanism in the regulation of plant cell physiology and development [1]. Therefore, auxin transport has been a matter of extensive interest and investigation ever since the emergence of the auxin concept more than a century ago [3]. Although seemingly a simple problem, it turned out to be very difficult to rigorously address the physiology and function of auxin transport proteins at the molecular level [4]: auxin transport studies have been found to be complicated by the diffusion component of auxins ([5], [6]; see Section 2 and Box 1). Moreover, membrane proteins are generally difficult to analyze functionally because of their low solubility at conditions that preserve their native structure and function. Thus, the energy-coupling mechanisms and activity regulation of auxin transporters have remained poorly understood. In contrast, significant progress has been made during the last several years in understanding the membrane targeting of auxin transporters and their effects on plant development [5]. Some advances have been also made toward the elucidation of the functional interactions of auxin transporters with additional regulatory proteins of the immunophilin class. These may affect auxin-transporter trafficking and/or activity [7], [8], [9], [10]. The progress in this more recent field is summarized and critically discussed here.
Section snippets
Auxin transport across biological membranes
According to the chemiosmotic model of auxin transport [11], [12], [13], [14], a substantial portion of IAA is protonated in the apoplast and able to enter cells via bilayer diffusion, whereas IAA inside the cells is less protonated and its efflux requires active transport. As to our knowledge, whether this is completely so has never been proven experimentally. In this context it is worth mentioning that drug leakage into cells by lipophilic diffusion versus hitchhiking of transporters is
Plant immunophilins are implicated in regulation of development
Immunophilins belong to two evolutionary non-related groups of proteins originally discovered and classified based on their ability to bind two different classes of immunosuppressant drugs: FK506-binding proteins (FKBPs) bind macrolides, FK506 (tacrolimus) and rapamycin (sirolimus), via their FK506-binding domain (FKBD) (see Fig. 1). Cyclophilins (also called rotamases and referred to either as Cyps, or ROCs for rotamase Cyps) are named after their high affinity for the cyclic peptide,
Functional interactions of immunophilins with auxin transporter proteins regulate auxin transport
The regulatory role of TWD1/FKBP42 on ABCB transporter activity and ABCB presence on the plasma membrane has been extensively documented [8], [9], [43], [44], [62]. ABCB1/PGP1 was identified in a yeast two-hybrid screen using TWD1 as bait [62], although a role of ABCB1 in hypocotyl elongation had been described earlier [27]. In heterologous auxin-transport systems, TWD1 strongly modulates the transport activity of ABCB1 [8], [43], [44], [62] and ABCB19 [43] (see Fig. 2). In agreement,
Imunophilins might mediate auxin transporter sensitivity to NPA
Auxin transport inhibitors, such as the synthetic non-competitive auxin efflux inhibitor NPA (1-N-naphthylphtalamic acid) and plant endogenous flavonoids (initially identified by their ability to replace NPA in plasma membrane binding [12]) inhibit auxin efflux through some poorly understood mechanisms. At low micromolar concentrations, auxin transport inhibitors are thought to impair directly the activity of auxin transporters [37], [41], [101], whereas at higher concentrations (>50 μM) auxin
Outlook
The analysis of auxin transport processes has made substantial progress in the last 20 years but has left us with a flurry of urgent questions. Currently, the functional significance of having both primary and secondary transporters for auxin is unclear, and we do need further mechanistic detail on their individual energization, interaction, and regulation. In particular, PIN and AUX1/LAX proteins share little similarity with transporters from non-plant systems, which prevents their structural
Acknowledgements
Financial support was provided by the Pool de Recherche of the University of Fribourg (M.G.), by the Novartis Foundation (M.G.), by Swiss National Funds (M.G.), by the USDA National Research Initiative Competitive Grants Program (2007-35304-17728 to M.G.I.) and by the Oregon State University General Research Fund (to M.G.I.).
References (137)
- et al.
Auxin: a trigger for change in plant development
Cell
(2009) - et al.
The ABC of auxin transport: the role of p-glycoproteins in plant development
FEBS Lett.
(2006) - et al.
Local, efflux-dependent auxin gradients as a common module for plant organ formation
Cell
(2003) - et al.
MDR-like ABC transporter AtPGP4 is involved in auxin-mediated lateral root and root hair development
FEBS Lett.
(2005) - et al.
Dynamic control of auxin transport-dependent growth by AGCVIII protein kinases
Curr. Opin. Plant Biol.
(2014) - et al.
Identification of an ABCB/P-glycoprotein-specific inhibitor of auxin transport by chemical genomics
J. Biol. Chem.
(2010) - et al.
Arabidopsis P-glycoprotein19 participates in the inhibition of gravitropism by gravacin
Chem. Biol.
(2007) - et al.
High-affinity auxin transport by the AUX1 influx carrier protein
Curr. Biol.
(2006) - et al.
Immunophilin-like TWISTED DWARF1 modulates auxin efflux activities of Arabidopsis P-glycoproteins
J. Biol. Chem.
(2006) - et al.
Modulation of P-glycoproteins by auxin transport inhibitors is mediated by interaction with immunophilins
J. Biol. Chem.
(2008)