Journal
JOURNAL OF CELL BIOLOGY
Volume 149, Issue 7, Pages 1345-1359Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.149.7.1345
Keywords
Zellweger syndrome; membrane biogenesis; protein import; vesicle traffic; peroxisome biogenesis disorders
Categories
Funding
- NICHD NIH HHS [P01 HD010981, HD10981] Funding Source: Medline
- NIDDK NIH HHS [R01 DK045787, DK45787] Funding Source: Medline
Ask authors/readers for more resources
In humans, defects in peroxisome biogenesis are the cause of lethal diseases typified by Zellweger syndrome. Here, we show that inactivating mutations in human PEX3 cause Zellweger syndrome, abrogate peroxisome membrane synthesis, and result in reduced abundance of peroxisomal membrane proteins (PMPs) and/or mislocalization of PMPs to the mitochondria. Previous studies have suggested that PEX3 may traffic through the ER en route to the peroxisome, that the COPI inhibitor, brefeldin A, leads to accumulation of PEX3 in the ER, and that PEX3 overexpression alters the morphology of the ER. However, we were unable to detect PEX3 in the ER at early times after expression. Furthermore, we find that inhibition of COPI function by brefeldin A has no effect on trafficking of PEX3 to peroxisomes and does not inhibit PEX3-mediated peroxisome biogenesis. We also find that inhibition of COPII-dependent membrane traffic by a dominant negative SAR1 mutant fails to block PEX3 transport to peroxisomes and PEX3-mediated peroxisome synthesis. Based on these results, we propose that PEX3 targeting to peroxisomes and PEX3-mediated peroxisome membrane synthesis may occur independently of COPI- and COPII-dependent membrane traffic.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available