PEX19 Binds Multiple Peroxisomal Membrane Proteins, Is Predominantly Cytoplasmic, and Is Required for Peroxisome Membrane Synthesis

doi:10.1083/jcb.148.5.931

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© The Rockefeller University Press, 0021-9525/2000/3/931/ $5.00
The Journal of Cell Biology, Volume 148, Number 5, March 6, 2000 931-944

Original Article

PEX19 Binds Multiple Peroxisomal Membrane Proteins, Is Predominantly Cytoplasmic, and Is Required for Peroxisome Membrane Synthesis

Katherine A. Sacksteder^a, Jacob M. Jones^a, Sarah T. South^a, Xiaoling Li^a, Yifei Liu^a, and Stephen J. Gould^a
^a Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Correspondence to: Stephen J. Gould, Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205. Tel:(410) 955-3085 Fax:(410) 955-0215

Peroxisomes are components of virtually all eukaryotic cells.While much is known about peroxisomal matrix protein import,our understanding of how peroxisomal membrane proteins (PMPs)are targeted and inserted into the peroxisome membrane is extremelylimited. Here, we show that PEX19 binds a broad spectrum ofPMPs, displays saturable PMP binding, and interacts with regionsof PMPs required for their targeting to peroxisomes. Furthermore,mislocalization of PEX19 to the nucleus leads to nuclear accumulationof newly synthesized PMPs. At steady state, PEX19 is bimodallydistributed between the cytoplasm and peroxisome, with mostof the protein in the cytoplasm. We propose that PEX19 may bindnewly synthesized PMPs and facilitate their insertion into theperoxisome membrane. This hypothesis is supported by the observationthat the loss of PEX19 results in degradation of PMPs and/ormislocalization of PMPs to the mitochondrion.

Key Words: Zellweger syndrome, organelle, peroxisome biogenesis receptor,protein import

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