Peroxisomes are single membrane-bound organelles that function to compartmentalize certain metabolic reactions critical to human and plant development. I am studying peroxisomal processes in the model plant Arabidopsis thaliana, with a focus the import of matrix proteins from the cytoplasm into the organelle matrix. This import depends on more than a dozen peroxin (PEX) proteins, with PEX5 and PEX7 serving as receptors that shuttle proteins bearing a peroxisome targeting sequence (PTS) into the organelle. PEX5 is the PTS1 receptor, PEX7 is the PTS2 receptor, and in both plants and mammals, PEX7 depends upon PEX5 binding to deliver PTS2 cargo into the peroxisome. I propose to elucidate the functions of Arabidopsis PEX7 in peroxisomal matrix protein import. I will characterize pex7 mutants isolated through forward and reverse genetic screens in physiological and biochemical assays. I will examine localization of various peroxisomally targeted GFP derivatives and endogenous peroxisomal enzymes in the pex7 mutants, and determine whether the pex7 mutations disrupt PEX7-cargo binding, PEX7-PEX5 interactions, or PEX7 stability. I will characterize the interactions between mutant and wild-type PEX7 and PEX5 derivatives using the yeast two-hybrid assay, overexpression studies, and double mutant analyses. Finally, I will explore an alternate means for targeting PEX7 for PEX5 binding. ? ? In humans, deficiencies in PEX7 and other peroxins underlie the peroxisomal biogenesis disorders, which are frequently lethal in early infancy. Successful completion of these experiments will advance our understanding of peroxisome biogenesis and metabolism in a genetically distinct model system, which will allow the continued refinement of our understanding of these essential organelles. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31GM081911-01
Application #
7323024
Study Section
Special Emphasis Panel (ZRG1-GGG-T (29))
Program Officer
Toliver, Adolphus
Project Start
2007-08-28
Project End
2010-08-27
Budget Start
2007-08-28
Budget End
2008-08-27
Support Year
1
Fiscal Year
2007
Total Cost
$26,257
Indirect Cost
Name
Rice University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
050299031
City
Houston
State
TX
Country
United States
Zip Code
77005
Monroe-Augustus, Melanie; Ramon, Naxhiely Martinez; Ratzel, Sarah E et al. (2011) Matrix proteins are inefficiently imported into Arabidopsis peroxisomes lacking the receptor-docking peroxin PEX14. Plant Mol Biol 77:1-15
Ramón, Naxhiely Martínez; Bartel, Bonnie (2010) Interdependence of the peroxisome-targeting receptors in Arabidopsis thaliana: PEX7 facilitates PEX5 accumulation and import of PTS1 cargo into peroxisomes. Mol Biol Cell 21:1263-71
Zolman, Bethany K; Martinez, Naxhiely; Millius, Arthur et al. (2008) Identification and characterization of Arabidopsis indole-3-butyric acid response mutants defective in novel peroxisomal enzymes. Genetics 180:237-51