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© The Rockefeller University Press,
0021-9525/2000//931 $5.00
The Journal of Cell Biology, Volume 148, Number 5,
, 2000 931-944
Original Article |
Pex19 Binds Multiple Peroxisomal Membrane Proteins, Is Predominantly Cytoplasmic, and Is Required for Peroxisome Membrane Synthesis
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 extremely limited. Here, we show that PEX19 binds a broad spectrum of PMPs, displays saturable PMP binding, and interacts with regions of PMPs required for their targeting to peroxisomes. Furthermore, mislocalization of PEX19 to the nucleus leads to nuclear accumulation of newly synthesized PMPs. At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of the protein in the cytoplasm. We propose that PEX19 may bind newly synthesized PMPs and facilitate their insertion into the peroxisome membrane. This hypothesis is supported by the observation that the loss of PEX19 results in degradation of PMPs and/or mislocalization of PMPs to the mitochondrion.
Key Words: Zellweger syndrome • organelle • peroxisome biogenesis receptor • protein import
© 2000 The Rockefeller University Press
Abbreviations used in this paper: AD, activation domain; BD, binding domain; NLS, nuclear localization signal; ORF, open reading frame; PMP, peroxisomal membrane protein; ZS, Zellweger syndrome.
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