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)

Research output: Contribution to journalArticle

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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 languageEnglish
Article numbere1006310
Pages (from-to)1-23
Number of pages23
JournalPLoS Pathogens
Volume13
Issue number4
DOIs
Publication statusPublished - 7 Apr 2017

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Kinetoplast DNA
Leucyl Aminopeptidase
Trypanosoma brucei brucei
Umbilicus
Cytokinesis
Metalloproteases
Mitochondrial DNA
Cell Cycle
Parasites
Proteins
Cell Proliferation

Keywords

  • Journal article

Cite this

Peña-Diaz, Priscila ; Vancová, Marie ; Resl, Christian ; Field, Mark C. ; Lukeš, Julius. / A leucine aminopeptidase is involved in kinetoplast DNA segregation in Trypanosoma brucei. In: PLoS Pathogens. 2017 ; Vol. 13, No. 4. pp. 1-23.
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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.",
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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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A leucine aminopeptidase is involved in kinetoplast DNA segregation in Trypanosoma brucei. / Peña-Diaz, Priscila; Vancová, Marie; Resl, Christian; Field, Mark C.; Lukeš, Julius (Lead / Corresponding author).

In: PLoS Pathogens, Vol. 13, No. 4, e1006310, 07.04.2017, p. 1-23.

Research output: Contribution to journalArticle

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T1 - A leucine aminopeptidase is involved in kinetoplast DNA segregation in Trypanosoma brucei

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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