A leucine aminopeptidase is involved in kinetoplast DNA segregation in Trypanosoma brucei

Priscila Peña-Diaz; Marie Vancová; Christian Resl; Mark C. Field; Julius Lukeš

doi:10.1371/journal.ppat.1006310

A leucine aminopeptidase is involved in kinetoplast DNA segregation in Trypanosoma brucei

Priscila Peña-Diaz, Marie Vancová, Christian Resl, Mark C. Field, Julius Lukeš (Lead / Corresponding author)

Biological Chemistry and Drug Discovery

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Abstract

The kinetoplast (k), the uniquely packaged mitochondrial DNA of trypanosomatid protists is formed by a catenated network of minicircles and maxicircles that divide and segregate once each cell cycle. Although many proteins involved in kDNA replication and segregation are now known, several key steps in the replication mechanism remain uncharacterized at the molecular level, one of which is the nabelschnur or umbilicus, a prominent structure which in the mammalian parasite Trypanosoma brucei connects the daughter kDNA networks prior to their segregation. Here we characterize an M17 family leucyl aminopeptidase metalloprotease, termed TbLAP1, which specifically localizes to the kDNA disk and the nabelschur and represents the first described protein found in this structure. We show that TbLAP1 is required for correct segregation of kDNA, with knockdown resulting in delayed cytokinesis and ectopic expression leading to kDNA loss and decreased cell proliferation. We propose that TbLAP1 is required for efficient kDNA division and specifically participates in the separation of daughter kDNA networks.

Original language	English
Article number	e1006310
Pages (from-to)	1-23
Number of pages	23
Journal	PLoS Pathogens
Volume	13
Issue number	4
DOIs	https://doi.org/10.1371/journal.ppat.1006310
Publication status	Published - 7 Apr 2017

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Journal article

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10.1371/journal.ppat.1006310Licence: CC BY

Final Published Version
© 2017 Peña-Diaz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Final published version, 4.26 MBLicence: CC BY

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title = "A leucine aminopeptidase is involved in kinetoplast DNA segregation in Trypanosoma brucei",

abstract = "The kinetoplast (k), the uniquely packaged mitochondrial DNA of trypanosomatid protists is formed by a catenated network of minicircles and maxicircles that divide and segregate once each cell cycle. Although many proteins involved in kDNA replication and segregation are now known, several key steps in the replication mechanism remain uncharacterized at the molecular level, one of which is the nabelschnur or umbilicus, a prominent structure which in the mammalian parasite Trypanosoma brucei connects the daughter kDNA networks prior to their segregation. Here we characterize an M17 family leucyl aminopeptidase metalloprotease, termed TbLAP1, which specifically localizes to the kDNA disk and the nabelschur and represents the first described protein found in this structure. We show that TbLAP1 is required for correct segregation of kDNA, with knockdown resulting in delayed cytokinesis and ectopic expression leading to kDNA loss and decreased cell proliferation. We propose that TbLAP1 is required for efficient kDNA division and specifically participates in the separation of daughter kDNA networks.",

keywords = "Journal article",

author = "Priscila Pe{\~n}a-Diaz and Marie Vancov{\'a} and Christian Resl and Field, {Mark C.} and Julius Luke{\v s}",

note = "This work was supported by project Bioglobe (CZ1.07/2.3.00/30.0032; http://alfa.bc.cas.cz/en/Postdok-BIOGLOBE/project-description/) to PPD and JL, by the Czech Grant Agency award (16-18699S; https://gacr.cz/) to JL, the COST action (CA15133; http://www.cost.eu/COST_Actions) to JL and MR/K008749/1, MR/N010558/1, MR/P009018/1 from MRC (mrc.ac.uk) and 204697/Z/16/Z from Wellcome (wellcome.ac.uk) to MCF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.",

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AU - Peña-Diaz, Priscila

AU - Vancová, Marie

AU - Resl, Christian

AU - Field, Mark C.

AU - Lukeš, Julius

N1 - This work was supported by project Bioglobe (CZ1.07/2.3.00/30.0032; http://alfa.bc.cas.cz/en/Postdok-BIOGLOBE/project-description/) to PPD and JL, by the Czech Grant Agency award (16-18699S; https://gacr.cz/) to JL, the COST action (CA15133; http://www.cost.eu/COST_Actions) to JL and MR/K008749/1, MR/N010558/1, MR/P009018/1 from MRC (mrc.ac.uk) and 204697/Z/16/Z from Wellcome (wellcome.ac.uk) to MCF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

PY - 2017/4/7

Y1 - 2017/4/7

N2 - The kinetoplast (k), the uniquely packaged mitochondrial DNA of trypanosomatid protists is formed by a catenated network of minicircles and maxicircles that divide and segregate once each cell cycle. Although many proteins involved in kDNA replication and segregation are now known, several key steps in the replication mechanism remain uncharacterized at the molecular level, one of which is the nabelschnur or umbilicus, a prominent structure which in the mammalian parasite Trypanosoma brucei connects the daughter kDNA networks prior to their segregation. Here we characterize an M17 family leucyl aminopeptidase metalloprotease, termed TbLAP1, which specifically localizes to the kDNA disk and the nabelschur and represents the first described protein found in this structure. We show that TbLAP1 is required for correct segregation of kDNA, with knockdown resulting in delayed cytokinesis and ectopic expression leading to kDNA loss and decreased cell proliferation. We propose that TbLAP1 is required for efficient kDNA division and specifically participates in the separation of daughter kDNA networks.

AB - The kinetoplast (k), the uniquely packaged mitochondrial DNA of trypanosomatid protists is formed by a catenated network of minicircles and maxicircles that divide and segregate once each cell cycle. Although many proteins involved in kDNA replication and segregation are now known, several key steps in the replication mechanism remain uncharacterized at the molecular level, one of which is the nabelschnur or umbilicus, a prominent structure which in the mammalian parasite Trypanosoma brucei connects the daughter kDNA networks prior to their segregation. Here we characterize an M17 family leucyl aminopeptidase metalloprotease, termed TbLAP1, which specifically localizes to the kDNA disk and the nabelschur and represents the first described protein found in this structure. We show that TbLAP1 is required for correct segregation of kDNA, with knockdown resulting in delayed cytokinesis and ectopic expression leading to kDNA loss and decreased cell proliferation. We propose that TbLAP1 is required for efficient kDNA division and specifically participates in the separation of daughter kDNA networks.

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DO - 10.1371/journal.ppat.1006310

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JO - PLoS Pathogens

JF - PLoS Pathogens

IS - 4

M1 - e1006310

ER -

A leucine aminopeptidase is involved in kinetoplast DNA segregation in Trypanosoma brucei

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