HSP90 differentially stabilizes plant ABCB-type auxin transporters on the plasma membrane

Tashi Tsering, Martin Donato, Despina Samakovli, Dimitra Milioni, Francesca Romana Iacobini, Konstantinos Panagiotopoulos, Panagiota-Konstantinia Plitsi, Elisa Azarello, Stefano Mancuso, Vendula Pukyšová, Marta Zwiewka, Tomasz Nodzynski, Michael Stumpe, Jutta Ludwig-Müller, Aurélien Bailly, Polydefkis Hatzopoulos () and Markus M. Geisler ()
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Tashi Tsering: University of Fribourg, Department of Biology
Martin Donato: University of Fribourg, Department of Biology
Despina Samakovli: Agricultural University of Athens, School of Applied Biology and Biotechnology, Department of Biotechnology
Dimitra Milioni: Agricultural University of Athens, School of Applied Biology and Biotechnology, Department of Biotechnology
Francesca Romana Iacobini: University of Fribourg, Department of Biology
Konstantinos Panagiotopoulos: Agricultural University of Athens, School of Applied Biology and Biotechnology, Department of Biotechnology
Panagiota-Konstantinia Plitsi: Agricultural University of Athens, School of Applied Biology and Biotechnology, Department of Biotechnology
Elisa Azarello: Università di Firenze
Stefano Mancuso: Università di Firenze
Vendula Pukyšová: Mendel Centre for Plant Genomics and Proteomics Masaryk University, CEITEC MU
Marta Zwiewka: Mendel Centre for Plant Genomics and Proteomics Masaryk University, CEITEC MU
Tomasz Nodzynski: Mendel Centre for Plant Genomics and Proteomics Masaryk University, CEITEC MU
Michael Stumpe: University of Fribourg, Department of Biology
Jutta Ludwig-Müller: Technische Universität Dresden, Faculty of Biology
Aurélien Bailly: University of Zürich
Polydefkis Hatzopoulos: Agricultural University of Athens, School of Applied Biology and Biotechnology, Department of Biotechnology
Markus M. Geisler: University of Fribourg, Department of Biology

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Closely related FKBP orthologs, FKBP42/TWISTED DWARF1 (TWD1) and FKBP38, have been shown to control the biogenesis of plant and mammalian ATP-binding cassette (ABC) transporters, respectively. However, the mechanistic role of the described FKBP-ABCB interaction is widely unknown. Here, we verify cytosolic HEAT-SHOCK PROTEIN90 (HSP90) isoforms as valid interactors of TWD1 and map HSP90 binding to an amphiphilic alpha-helix preceding its TPR domain. We provide pharmacological and genetic evidence that a subset of TWD1-interacting ABCBs, in contrast to mammalian ABCBs, are constitutive HSP90 clients in plants. This effect and its specificity are presumably provided by TWD1. Our data strongly correlate the impact of HSP90 inhibition on ABCB-mediated development and ABCB plasma membrane stability on the one hand and ABCB cycling rate on the other. In summary, we uncover a dynamic mechanism of HSP90 for differential stabilization of the plasma membrane ABCB isoforms to regulate polar auxin transport and to confer developmental plasticity.

Date: 2025
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DOI: 10.1038/s41467-025-63780-w

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