TY  - JOUR
AU  - Bailly, A.
AU  - Sovero, V.
AU  - Vincenzetti, V.
AU  - Santelia, D.
AU  - Bartnik, D.
AU  - Koenig, B. W.
AU  - Mancuso, S.
AU  - Martinoia, E.
AU  - Geisler, M.
TI  - Modulation of P-glycoproteins by auxin transport inhibitors is mediated by interaction with immunophilins
JO  - The journal of biological chemistry
VL  - 283
SN  - 0021-9258
CY  - Bethesda, Md.
PB  - Soc.
M1  - PreJuSER-62894
SP  - 21817 - 21826
PY  - 2008
N1  - Record converted from VDB: 12.11.2012
AB  - The immunophilin-like FKBP42 TWISTED DWARF1 (TWD1) has been shown to control plant development via the positive modulation of ABCB/P-glycoprotein (PGP)-mediated transport of the plant hormone auxin. TWD1 functionally interacts with two closely related proteins, ABCB1/PGP1 and ABCB19/PGP19/MDR1, both of which exhibit the ability to bind to and be inhibited by the synthetic auxin transport inhibitor N-1-naphylphtalamic acid (NPA). They are also inhibited by flavonoid compounds, which are suspected modulators of auxin transport. The mechanisms by which flavonoids and NPA interfere with auxin efflux components are unclear. We report here the specific disruption of PGP1-TWD1 interaction by NPA and flavonoids using bioluminescence resonance energy transfer with flavonoids functioning as a classical established inhibitor of mammalian and plant PGPs. Accordingly, TWD1 was shown to mediate modulation of PGP1 efflux activity by these auxin transport inhibitors. NPA bound to both PGP1 and TWD1 but was excluded from the PGP1-TWD1 complex expressed in yeast, suggesting a transient mode of action in planta. As a consequence, auxin fluxes and gravitropism in twd1 roots are less affected by NPA treatment, whereas TWD1 gain-of-function promotes root bending. Our data support a novel model for the mode of drug-mediated P-glycoprotein regulation mediated via protein-protein interaction with immunophilin-like TWD1.
KW  - ATP-Binding Cassette Transporters: chemistry
KW  - Arabidopsis: metabolism
KW  - Arabidopsis Proteins: chemistry
KW  - Biological Transport
KW  - Cell Membrane: metabolism
KW  - Flavonoids: chemistry
KW  - Homozygote
KW  - Immunophilins: chemistry
KW  - Indoleacetic Acids: chemistry
KW  - Luminescence
KW  - Models, Biological
KW  - P-Glycoprotein: chemistry
KW  - P-Glycoproteins: chemistry
KW  - Plant Roots: metabolism
KW  - Protein Binding
KW  - Tacrolimus Binding Proteins: chemistry
KW  - ATP-Binding Cassette Transporters (NLM Chemicals)
KW  - ATPGP1 protein, Arabidopsis (NLM Chemicals)
KW  - Arabidopsis Proteins (NLM Chemicals)
KW  - Flavonoids (NLM Chemicals)
KW  - Indoleacetic Acids (NLM Chemicals)
KW  - P-Glycoprotein (NLM Chemicals)
KW  - P-Glycoproteins (NLM Chemicals)
KW  - TWD1 protein, Arabidopsis (NLM Chemicals)
KW  - Tacrolimus Binding Proteins (NLM Chemicals)
KW  - Immunophilins (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:18499676
UR  - <Go to ISI:>//WOS:000257898800055
DO  - DOI:10.1074/jbc.M709655200
UR  - https://juser.fz-juelich.de/record/62894
ER  -