Identification of trypanosomatid PEX19: functional characterization reveals impact on cell growth and glycosome size and number.

Abstract:

:Glycosomes are peroxisome-like organelles present in trypanosomatid pathogens. These organelles compartmentalize glycolysis, among other reactions, and are essential in both bloodstream and procyclic form Trypanosoma brucei. Peroxins (PEXs) are proteins necessary for biogenesis of peroxisomes and glycosomes. In each assembled trypanosomatid genome, we identified a predicted protein with approximately 20% sequence identity to human PEX19, a protein required for insertion of peroxisomal membrane proteins (PMPs) into the membrane. Functional analysis demonstrated that these proteins are indeed PEX19 orthologues. Like other PEX19s, T. brucei and Leishmania major PEX19 GFP fusion proteins are predominantly cytosolic. We further showed that LmPEX19 interacts with the glycosomal membrane protein PEX2 in the yeast two-hybrid system. Partial knockdown of TbPEX19 slowed parasite growth, particularly when glucose was present. Immunofluorescence and electron microscopic studies revealed biogenesis defect as evidenced by a sharp reduction in the number of glycosomes. Surprisingly, a four-fold increase in the size of the remaining glycosomes was observed. We propose that this phenotype of fewer but larger glycosomes results from the reduction in import of glycosomal membrane proteins.

journal_name

Mol Biochem Parasitol

authors

Banerjee SK,Kessler PS,Saveria T,Parsons M

doi

10.1016/j.molbiopara.2005.03.008

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

47-55

issue

1

eissn

0166-6851

issn

1872-9428

pii

S0166-6851(05)00104-0

journal_volume

142

pub_type

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