A twist in the ABC: regulation of ABC transporter trafficking and transport by FK506-binding proteins

Markus Geisler; Tamás Hegedűs

doi:10.1002/1873-3468.13983

A twist in the ABC: regulation of ABC transporter trafficking and transport by FK506-binding proteins

FEBS Lett. 2020 Dec;594(23):3986-4000. doi: 10.1002/1873-3468.13983. Epub 2020 Nov 13.

Authors

Markus Geisler¹, Tamás Hegedűs²

Affiliations

¹ Department of Biology, University of Fribourg, Switzerland.
² Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.

PMID: 33125703
DOI: 10.1002/1873-3468.13983

Abstract

Post-transcriptional regulation of ATP-binding cassette (ABC) proteins has been so far shown to encompass protein phosphorylation, maturation, and ubiquitination. Yet, recent accumulating evidence implicates FK506-binding proteins (FKBPs), a type of peptidylprolyl cis-trans isomerase (PPIase) proteins, in ABC transporter regulation. In this perspective article, we summarize current knowledge on ABC transporter regulation by FKBPs, which seems to be conserved over kingdoms and ABC subfamilies. We uncover striking functional similarities but also differences between regulatory FKBP-ABC modules in plants and mammals. We dissect a PPIase- and HSP90-dependent and independent impact of FKBPs on ABC biogenesis and transport activity. We propose and discuss a putative new mode of transient ABC transporter regulation by cis-trans isomerization of X-prolyl bonds.

Keywords: ABC transporters; ABCB; CFTR; FKBP; FKBP38; HSP90; PPIase; TWD1; chaperon.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

ATP Binding Cassette Transporter, Subfamily B / chemistry
ATP Binding Cassette Transporter, Subfamily B / metabolism
ATP-Binding Cassette Sub-Family B Member 4
ATP-Binding Cassette Transporters / biosynthesis
ATP-Binding Cassette Transporters / chemistry
ATP-Binding Cassette Transporters / classification
ATP-Binding Cassette Transporters / metabolism*
Animals
Biological Transport
Cystic Fibrosis Transmembrane Conductance Regulator / biosynthesis
Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
HSP90 Heat-Shock Proteins / metabolism
Humans
Immunophilins / metabolism
Models, Molecular
Proline / metabolism
Tacrolimus Binding Protein 1A / metabolism
Tacrolimus Binding Proteins / metabolism*

Substances

ATP Binding Cassette Transporter, Subfamily B
ATP-Binding Cassette Transporters
CFTR protein, human
FKBP8 protein, human
HSP90 Heat-Shock Proteins
Cystic Fibrosis Transmembrane Conductance Regulator
Proline
Tacrolimus Binding Protein 1A
Tacrolimus Binding Proteins
Immunophilins

Associated data

RefSeq/NP_181228