Functional diversity and bilobe targeting by the MORN Domain Proteins of Leishmania major

Jobe, Momodou (2015) Functional diversity and bilobe targeting by the MORN Domain Proteins of Leishmania major. Masters thesis, University of East Anglia.

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Abstract

Leishmania is a protozoan parasite responsible for a spectrum of diseases known as leishmaniasis. The cell body of Leishmania consists of single copies of several organelles whose faithful duplication are crucial for survival. Previously, a novel cytoskeletal organelle called the bilobe was discovered while studying Golgi biogenesis in T. brucei. TbMORN1 became the first identified structural component of the bilobe with exclusive localization. TbMORN1 is composed of 15 MORN-repeats which may imply that the MORN-repeats are responsible for its bilobe targeting. Given that MORN proteins have only been characterized in T. brucei among the kinetoplastids, I chose to study the MORN proteins of L. major an important experimental model. 22 uncharacterized proteins were annotated to contain MORN-repeats in L. major, 14 of which share the feature of exclusively containing MORN-repeats ranging from 3-15 repeats, while the remaining 7 carry additional functional domains. The strategy was to express two apparently varied LmaMORNs (LmaMORN5 and LmaMORN6) from each other and from MORN1 in L. major promastigotes, screen them for bilobe localization and investigate their possible function. I showed that both LmaMORN5 and LmaMORN6 target the bilobe and the basal bodies while LmaMORN6 additionally stained the flagellum indicating flagellar function. These localizations were true even after detergent extraction, implying intimate associations with the bilobe and other cytoskeletal structures, hinting at a structural role. LmaMORN5 contained two compartmentalized regions along its sequence under selective pressure, shown to be secreted into the cytoplasm of infected macrophages and seemed to increased parasites infectivity six-fold, suggesting a possible role as a virulence factor. Thus, I reported for the first time two other MORN proteins (LmaMORN5 and LmaMORN6) in L. major that targets the bilobe in a manner similar to TbMORN1 in T. brucei, while each appear to display a differential functional role in the parasite’s biology.

Item Type:	Thesis (Masters)
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	Jackie Webb
Date Deposited:	18 Feb 2016 12:15
Last Modified:	18 Feb 2016 12:15
URI:	https://ueaeprints.uea.ac.uk/id/eprint/57166
DOI:

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