Abstract
Proteins destined for the peroxisomal matrix are targeted by virtue of a peroxisomal targeting sequence type 1 (PTS1) or type 2 (PTS2). In humans, targeting of either class of proteins relies on a cytosolic receptor protein encoded by the PEX5 gene. Alternative splicing of PEX5 results in two protein variants, PEX5S and PEX5L. PEX5S is exclusively involved in PTS1 protein import, whereas PEX5L mediates the import of both PTS1 and PTS2 proteins. Genetic complementation testing with over 500 different fibroblast cell lines from patients diagnosed with a peroxisome biogenesis disorder (PBD) identified 11 cell lines with a defect in PEX5. The aim of this study was to characterize these cell lines at a biochemical and genetic level. To this end, the cultured fibroblasts were analyzed for very long chain fatty acid (VLCFA) concentrations, peroxisomal beta-and alpha-oxidation, dihydroxyacetone-phosphate acyltransferase (DHAPAT) activity, peroxisomal thiolase, and catalase immunofluorescence. Mutation analysis of the PEX5 gene revealed 11 different mutations, eight of which are novel. PTS1- and PTS2-protein import capacity was assessed by transfection of the cells with green fluorescent protein (GFP) tagged with either PTS1 or PTS2. Si...Continue Reading
References
Jun 1, 1988·The Journal of Clinical Investigation·S BrulJ M Tager
Jan 1, 1985·Annual Review of Cell Biology·P B Lazarow, Y Fujiki
Feb 1, 1995·Nature Genetics·G DodtS J Gould
May 18, 1994·Biochimica Et Biophysica Acta·R Ofman, R J Wanders
Apr 23, 1993·Biochimica Et Biophysica Acta·R J Wanders, C W Van Roermund
Jan 1, 1995·Journal of Inherited Metabolic Disease·R J WandersP Mooijer
Jan 1, 1995·Journal of Inherited Metabolic Disease·R J WandersB S Jacobs
Jul 21, 1998·Human Molecular Genetics·N BravermanD Valle
Sep 24, 1998·Journal of Chromatography. B, Biomedical Sciences and Applications·P VrekenA H van Gennip
Jan 23, 1999·American Journal of Human Genetics·E G van GrunsvenR J Wanders
Aug 27, 1999·Biochemical and Biophysical Research Communications·N ShimozawaN Kondo
Apr 18, 2000·The Journal of Biological Chemistry·T MatsumuraY Fujiki
Dec 2, 2000·Nature Structural Biology·G J GattoJ M Berg
Jul 5, 2001·The Journal of Biological Chemistry·J SaidowskyW Schliebs
Sep 8, 2001·The Journal of Biological Chemistry·G DodtS J Gould
Feb 28, 2002·Molecular and Cellular Biology·Hidenori OteraYukio Fujiki
Dec 11, 2002·Neurology·J GootjesR J A Wanders
Oct 7, 2003·Annual Review of Genomics and Human Genetics·Sabine WellerDavid Valle
Jun 8, 2006·Annual Review of Biochemistry·Ronald J A Wanders, Hans R Waterham
Oct 24, 2006·Biochimica Et Biophysica Acta·Steven J SteinbergHugo W Moser
Dec 13, 2006·Molecular Cell·Will A StanleyMatthias Wilmanns
Apr 13, 2007·BMC Structural Biology·Will A StanleyPetri Kursula
Apr 21, 2007·FEBS Letters·Harald W Platta, Ralf Erdmann
Apr 25, 2007·The Journal of Cell Biology·Harald W PlattaRalf Erdmann
May 29, 2007·Biochimica Et Biophysica Acta·Andreia F CarvalhoJorge E Azevedo
May 31, 2007·Journal of Human Genetics·Avraham ZehariaStanley H Korman
Citations
Dec 15, 2010·Cell Stress & Chaperones·Rudi Kenneth Allan, Thomas Ratajczak
Mar 12, 2011·Orphanet Journal of Rare Diseases·Caroline SevinPatrick Aubourg
Jul 17, 2010·The International Journal of Biochemistry & Cell Biology·Chris P Williams, Will A Stanley
Oct 30, 2010·Human Mutation·Merel S EbberinkHans R Waterham
Feb 12, 2010·Biology of the Cell·Thomas Lanyon-HoggAlison Baker
Oct 10, 2015·Biochimica Et Biophysica Acta·Leonidas EmmanouilidisMichael Sattler
Jul 30, 2015·Human Molecular Genetics·Tuva BarøyEirik Frengen
Aug 9, 2012·Biochimica Et Biophysica Acta·Hans R Waterham, Merel S Ebberink
Jun 12, 2016·Molecular Ecology·Baocheng GuoJuha Merilä
Nov 12, 2016·Biochemical and Biophysical Research Communications·Valentina PianoAndrea Mattevi
Sep 22, 2017·Cell Cycle·Wei Wang, Suresh Subramani
Nov 24, 2017·Physiological Reviews·Cheryl L WalkerKelvin J A Davies
Jan 4, 2021·Human Genetics·Muhammad AliS Amer Riazuddin