title: Mammalian farnesyltransferase α subunit regulates vacuolar protein sorting-associated protein 4A (Vps4A)--dependent intracellular trafficking through recycling endosomes.
abstract: The protein farnesyltransferase (FTase) mediates posttranslational modification of proteins with isoprenoid lipids. FTase is a heterodimer and although the β subunit harbors the active site, it requires the α subunit for its activity. Here we explore the other functions of the FTase α subunit in addition to its established role in protein prenylation. We found that in the absence of the β subunit, the α subunit of FTase forms a stable autonomous dimeric structure in solution. We identify interactors of FTase α using mass spectrometry, followed by rapid in vitro analysis using the Leishmania tarentolae cell - free system. Vps4A was validated for direct binding to the FTase α subunit both in vitro and in vivo. Analysis of the interaction with Vps4A in Hek 293 cells demonstrated that FTase α controls trafficking of transferrin receptor upstream of this protein. These results point to the existence of previously undetected biological functions of the FTase α subunit that includes control of intracellular membrane trafficking.
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, St. Lucia, Queensland, 4072, Australia.
authors.forename: Marta H
authors.initials: MH
authors.lastname: Kubala
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, St. Lucia, Queensland, 4072, Australia.
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Norwood
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, St. Lucia, Queensland, 4072, Australia.
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Gomez
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, St. Lucia, Queensland, 4072, Australia.
authors.forename: Alun
authors.initials: A
authors.lastname: Jones
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, St. Lucia, Queensland, 4072, Australia.
authors.forename: Wayne
authors.initials: W
authors.lastname: Johnston
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, St. Lucia, Queensland, 4072, Australia.
authors.forename: Alpha S
authors.initials: AS
authors.lastname: Yap
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, St. Lucia, Queensland, 4072, Australia.
authors.forename: Sergey
authors.initials: S
authors.lastname: Mureev
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, St. Lucia, Queensland, 4072, Australia. Electronic address: k.alexandrov@uq.edu.au.
authors.forename: Kirill
authors.initials: K
authors.lastname: Alexandrov
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D011992:Endosomes / Q000502:physiology*; D051231:Farnesyltranstransferase / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D021122:Protein Subunits; D021381:Protein Transport / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D021122:Protein Subunits; D051231:Farnesyltranstransferase; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C490304:VPS4B protein, human
keywords: Farnesyltransferase; Isoprenylation; Oligomerization; Trafficking