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First published online June 8, 2006
doi: 10.1242/10.1242/jcs.02979

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Targeting of the tail-anchored peroxisomal membrane proteins PEX26 and PEX15 occurs through C-terminal PEX19-binding sites

¹ Institut für Physiologische Chemie, Abt. Systembiochemie, Ruhr-Universität Bochum, 44780 Bochum, Germany
² Institut für Medizinische Immunologie, Universitätsklinikum Charité, 10115 Berlin, Germany
³ Institut für Biochemie, Universitätsklinikum Charité, 10115 Berlin, Germany

^* Authors for correspondence (e-mail: Ralf.Erdmann{at}rub.de; Hanspeter.Rottensteiner{at}rub.de)

Accepted 16 March 2006

Tail-anchored proteins contain a single transmembrane domain (TMD) followed by a short C-terminal domain extending into the organellar lumen. Tail-anchored proteins are thought to target to the correct subcellular compartment by virtue of general physicochemical properties of their C-termini; however, the machineries that enable correct sorting remain largely elusive. Here we analyzed targeting of the human peroxisomal tail-anchored protein PEX26. Its C-terminal-targeting signal contains two binding sites for PEX19, the import receptor for several peroxisomal membrane proteins. One PEX19-binding site overlapped with the TMD, the other was contained within the luminal domain. Although the PEX19-binding site containing the TMD targeted to peroxisomes to some extent, the luminal site proved essential for correct targeting of the full-length protein, as it prevented PEX26 from mislocalization to mitochondria. Its function as a targeting motif was proved by its ability to insert a heterologous TMD-containing fragment into the peroxisomal membrane. Finally we show that PEX19 is essential for PEX26 import. Analysis of the yeast tail-anchored protein Pex15p revealed that it also harbors a luminal PEX19-binding site that acts as a peroxisomal-targeting motif. We conclude that C-terminal PEX19-binding sites mark tail-anchored proteins for delivery to peroxisomes.

Key words: Posttranslational protein import, Peroxisome biogenesis, Peroxin, Endoplasmic reticulum, Peroxisomal targeting signal, FIS1

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