Elsevier

Plant Science

Volume 245, April 2016, Pages 1-10
Plant Science

Review article
Master and servant: Regulation of auxin transporters by FKBPs and cyclophilins

https://doi.org/10.1016/j.plantsci.2015.12.004Get rights and content

Highlights

  • Plant immunophilins are implicated in developmental processes.

  • Interactions of immunophilins with auxin transporters regulate auxin transport.

  • Interactions affect membrane trafficking and thus activity of auxin transporters.

  • Immunophilins might integrate the action of auxin transport inhibitors on auxin transporters.

Abstract

Plant development and architecture are greatly influenced by the polar distribution of the essential hormone auxin. The directional influx and efflux of auxin from plant cells depends primarily on AUX1/LAX, PIN, and ABCB/PGP/MDR families of auxin transport proteins. The functional analysis of these proteins has progressed rapidly within the last decade thanks to the establishment of heterologous auxin transport systems. Heterologous co-expression allowed also for the testing of protein–protein interactions involved in the regulation of transporters and identified relationships with members of the FK506-Binding Protein (FKBP) and cyclophilin protein families, which are best known in non-plant systems as cellular receptors for the immunosuppressant drugs, FK506 and cyclosporin A, respectively. Current evidence that such interactions affect membrane trafficking, and potentially the activity of auxin transporters is reviewed. We also propose that FKBPs andcyclophilins might integrate the action of auxin transport inhibitors, such as NPA, on members of the ABCB and PIN family, respectively. Finally, we outline open questions that might be useful for further elucidation of the role of immunophilins as regulators (servants) of auxin transporters (masters).

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)

  • E. El Khouri et al.

    Functional interaction of the cystic fibrosis transmembrane conductance regulator with members of the SLC26 family of anion transporters (SLC26A8 and SLC26A9): physiological and pathophysiological relevance

    Int. J. Biochem. Cell Biol.

    (2014)
  • D. Vasudevan et al.

    Plant immunophilins: a review of their structure–function relationship

    Biochim. Biophys. Acta

    (2015)
  • B. Adams et al.

    A novel class of dual-family immunophilins

    J. Biol. Chem.

    (2005)
  • M. Geisler et al.

    Tete-a-tete: the function of FKBPs in plant development

    Trends Plant Sci.

    (2007)
  • D. Mok et al.

    The chaperone function of cyclophilin 40 maps to a cleft between the prolyl isomerase and tetratricopeptide repeat domains

    FEBS Lett.

    (2006)
  • X.C. Zhang et al.

    PPIase independent chaperone-like function of recombinant human Cyclophilin A during arginine kinase refolding

    FEBS Lett.

    (2013)
  • P. Wang et al.

    The cyclophilins

    Genome Biol.

    (2005)
  • C. Smyczynski et al.

    The C terminus of the immunophilin PASTICCINO1 is required for plant development and for interaction with a NAC-like transcription factor

    J. Biol. Chem.

    (2006)
  • Y. Harrar et al.

    FKBPs: at the crossroads of folding and transduction

    Trends Plant Sci.

    (2001)
  • V. Lippuner et al.

    Cloning and characterization of chloroplast and cytosolic forms of cyclophilin from Arabidopsis thaliana

    J. Biol. Chem.

    (1994)
  • F. Mignolli et al.

    Tomato fruit development in the auxin-resistant dgt mutant is induced by pollination but not by auxin treatment

    J. Plant Physiol.

    (2012)
  • C.S. Hemenway et al.

    Immunosuppressant target protein FKBP12 is required for P-glycoprotein function in yeast

    J. Biol. Chem.

    (1996)
  • Y.K. Banasavadi-Siddegowda et al.

    FKBP38 peptidylprolyl isomerase promotes the folding of cystic fibrosis transmembrane conductance regulator in the endoplasmic reticulum

    J. Biol. Chem.

    (2011)
  • J.G. Dubrovsky et al.

    Auxin acts as a local morphogenetic trigger to specify lateral root founder cells

    Proc. Natl. Acad. Sci. U. S. A.

    (2008)
  • C. Darwin et al.

    The Power of Movements in Plants

    (1880)
  • P. Grones et al.

    Auxin transporters and binding proteins at a glance

    J. Cell Sci.

    (2015)
  • M. Geisler et al.

    Cellular efflux of auxin catalyzed by the Arabidopsis MDR/PGP transporter AtPGP1

    Plant J.: Cell Mol. Biol.

    (2005)
  • J. Zhu et al.

    Keeping it all together: auxin–actin crosstalk in plant development

    J. Exp. Bot.

    (2015)
  • B. Wang et al.

    Arabidopsis twisted dwarf1 functionally interacts with auxin exporter ABCB1 on the root plasma membrane

    Plant Cell

    (2013)
  • G. Wu et al.

    The ER-localized TWD1 immunophilin is necessary for localization of multidrug resistance-like proteins required for polar auxin transport in Arabidopsis roots

    Plant Cell

    (2010)
  • M.G. Ivanchenko et al.

    The cyclophilin A DIAGEOTROPICA gene affects auxin transport in both root and shoot to control lateral root formation

    Development

    (2015)
  • T.L. Lomax et al.

    Auxin transport

  • M. Jacobs et al.

    Naturally-occurring auxin transport regulators

    Science

    (1988)
  • P.H. Rubery et al.

    Carrier-mediated auxin transport

    Planta

    (1974)
  • P.H. Rubery et al.

    Effect of pH and surface charge on cell uptake of auxin

    Nat. New Biol.

    (1973)
  • D.B. Kell et al.

    How drugs get into cells: tested and testable predictions to help discriminate between transporter-mediated uptake and lipoidal bilayer diffusion

    Front Pharmacol.

    (2014)
  • M. Geisler et al.

    Auxin transport during root gravitropism: transporters and techniques

    Plant Biol.

    (2014)
  • I. Blilou et al.

    The PIN auxin efflux facilitator network controls growth and patterning in Arabidopsis roots

    Nature

    (2005)
  • J.J. Blakeslee et al.

    Interactions among pin-formed and P-glycoprotein auxin transporters in Arabidopsis

    Plant Cell

    (2007)
  • J. Mravec et al.

    Interaction of PIN and PGP transport mechanisms in auxin distribution-dependent development

    Development

    (2008)
  • A. Bandyopadhyay et al.

    Interactions of PIN and PGP auxin transport mechanisms

    Biochem. Soc. Trans.

    (2007)
  • E. Zazimalova et al.

    Auxin transporters—why so many?

    Cold Spring Harb. Perspect. Biol.

    (2010)
  • M.J. Bennett et al.

    Arabidopsis AUX1 gene: a permease-like regulator of root gravitropism

    Science

    (1996)
  • I.D. Kerr et al.

    New insight into the biochemical mechanisms regulating auxin transport in plants

    Biochem. J.

    (2007)
  • K. Terasaka et al.

    PGP4 an ATP binding cassette P-glycoprotein, catalyzes auxin transport in Arabidopsis thaliana roots

    Plant Cell

    (2005)
  • M. Sidler et al.

    Involvement of an ABC transporter in a developmental pathway regulating hypocotyl cell elongation in the light

    Plant Cell

    (1998)
  • Y. Kamimoto et al.

    Arabidopsis ABCB21 is a facultative auxin importer/exporter regulated by cytoplasmic auxin concentration

    Plant Cell Physiol.

    (2012)
  • C. Luschnig et al.

    The dynamics of plant plasma membrane proteins: PINs and beyond

    Development

    (2014)
  • U. Kania et al.

    Polar delivery in plants, commonalities and differences to animal epithelial cells

    Open Biol.

    (2014)
  • Z. Ding et al.

    ER-localized auxin transporter PIN8 regulates auxin homeostasis and male gametophyte development in Arabidopsis

    Nat. Commun.

    (2012)
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