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Published online 11 June 2001. doi:10.1083/jcb.153.6.1141
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© The Rockefeller University Press, 0021-9525/2001//1141 $5.00
The Journal of Cell Biology, Volume 153, Number 6, , 2001 1141-1150

Original Article

Multiple Distinct Targeting Signals in Integral Peroxisomal Membrane Proteins



Jacob M. Jonesa, James C. Morrella, and Stephen J. Goulda

a The Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
The Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.(410) 955-0215(410) 955-3085

sgould{at}jhmi.edu

Peroxisomal proteins are synthesized on free polysomes and then transported from the cytoplasm to peroxisomes. This process is mediated by two short well-defined targeting signals in peroxisomal matrix proteins, but a well-defined targeting signal has not yet been described for peroxisomal membrane proteins (PMPs). One assumption in virtually all prior studies of PMP targeting is that a given protein contains one, and only one, distinct targeting signal. Here, we show that the metabolite transporter PMP34, an integral PMP, contains at least two nonoverlapping sets of targeting information, either of which is sufficient for insertion into the peroxisome membrane. We also show that another integral PMP, the peroxin PEX13, also contains two independent sets of peroxisomal targeting information. These results challenge a major assumption of most PMP targeting studies. In addition, we demonstrate that PEX19, a factor required for peroxisomal membrane biogenesis, interacts with the two minimal targeting regions of PMP34. Together, these results raise the interesting possibility that PMP import may require novel mechanisms to ensure the solubility of integral PMPs before their insertion in the peroxisome membrane, and that PEX19 may play a central role in this process.

Key Words: peroxisome • organelle biogenesis • PEX19 • targeting signal • PMP34

© 2001 The Rockefeller University Press

Abbreviations used in this paper: HA, hemagglutinin; NLS, nuclear localization signal; PMP, peroxisomal membrane protein; PTS, peroxisome-targeting signal.


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