Lundep increases leishmania parasite survival inside neutrophils

Leishmaniasis or kala azar is a disease caused by the parasite Leishmania, which belongs to lower eukaryotes. The bite of an insect Lutzomyia longipalpis aids in the transmission of the parasite to complete its life cycle.

In earlier studies it has been shown that the components of saliva (like hyaluronidase) from this arthropod aid in the transmission of Leishmania in host systems. However authors here have shown that another protein Lundep is also an active constituent of saliva for enhancing the parasite infection.

Since the first line of defense is by neutrophils and it has been established in case of Leishmaniasis that the parasites dodge this line of defense by entering into the compartments that are nonlytic or by dodging neutrophil extracellular traps (NETs).  Salivary Gland Extracts (SGE) from Lutzomyia longipalpis are known to support parasite survival inside the neutrophils, however still less is known about the NETosis or NET formation in respose to Leishmania parasite.

Lundep (Lutzomyia NET destroying protein), a female specific endonuclease has been shown in this study to have enhancing effect on the infectivity as well as inhibitory effect on intrinsic coagulation pathway. It has been demonstrated that catalytic activity of the salivary endonuclease is accountable for enhancing infectivity or in aiding parasites escape from NETs.

One Two

This study has shown that Lundep:-

  1. Aids in degradation of the DNA scaffold of NETs. [Lundep has a DNase activity of about 300000 Kunitz units per mg of protein and can hydrolise both single stranded and double-stranded DNA.]
  2. Protects parasites from leishmanicidal activity of NETs.
  3. Promotes survival of promastigotes.
  4. Prevents blood coagulation while insect biting. [ Lundep is shown to have DNase activity that promotes antithrombotic effects]
  5. Assists in taking blood meal by decreasing the viscosity at the site of bite. [At the site of bite viscosity augments due to host DNA release]

So far no vaccine is available for Leishmaniasis (kala azar) and the authors consider Lundep as a potential target for vaccine generation.

Reference Used:

Lundep, a Sand Fly Salivary Endonuclease Increases Leishmania Parasite Survival in Neutrophils and Inhibits XIIa Contact Activation in Human Plasma. Andrezza C. Chagas, Fabiano Oliveira, Alain Debrabant, Jesus G. Valenzuela, José M. C. Ribeiro, Eric Calvo.  DOI: 10.1371/journal.ppat.1003923

Advertisements

Elucidation of localization of long non coding RNA in different subcellular compartments

Research has proven the role of noncoding RNA transcripts in various cellular processes which includes telomeric maintenance and chromosome silencing. Although in past decade researchers have identified many long non protein coding RNA transcripts, but the functional role of most of them is still in its infancy.

The sub-cellular localization of lncRNAs is of utmost importance in order to elucidate or account for their functional utilities. Researchers have tried to explore lncRNAs abundance in various compartments within the cellular systems. About 17 percent of lncRNAs are known to occur in nuclear compartment, were as only 4 percent occur in cytosol. This observation is for some of the RNAs that are thought to be involved in nuclear structural organization and gene-expression regulation, e.g., MALAT1 and NEAT1. Moreover ribosomal association of cytosolic lncRNAs is also known. Despite having all this knowledge about lncRNAs, there is a lack of data that could really support this relative lncRNA species abundance in compartments like nucleus, cytosol and ribosomes.

A team of researches at the Netherlands has used sub-cellular RNA-seq and ribosomal fractionation methods in combination with microarray technique to elucidate the exact compartmental locations of the lncRNAs.

From the different sub-cellular sample fractions the authors have considered three transcript types only: sncRNAs, lncRNAs and protein-coding transcripts and excluded miRNAs. In overall the expressed transcript set contained 7734 number of genes, out of which 7206 genes were protein-coding, 152 genes were lncRNAs and 376 genes were sncRNAs. However despite having different compositions of sub-cellular samples, the authors conclude that lncRNAs are existent in each of them. Despite these findings some questions raised, that how the individual transcripts distribute among different sub-cellular sample fractions? And how these lncRNA species behave in a different way as judged against normal coding transcripts? In order to find answers to these queries an investigation was done to find the correlation of the distribution of every lncRNA across the sub-cellular fractions and every coding transcript. Experimentation revealed that the association is complex. However authors have tried to simplify it by using a clustering model wherein a total of eleven individual clusters were made. The first ten clusters (I-X) contained genes showing specific sub-cellular localization, but cluster XI did not demonstrate enrichment anywhere in any of the samples. Nuclear enrichment was found for clusters I, II and III; ribosome-free cytosol compartmentalization for clusters IV and V; and ribosome enrichment for clusters VI to X. Cluster III contained majority of sncRNAs that suggested shuttling of these RNAs between cytosol and nucleus. In terms of percentage about 30% of the lncRNAs were found in ribosome-free cytosol and 38% in ribosome-enriched clusters.

Apart from this some known lncRNAs like MALAT1, NEAT1 and TUG1 were found localized in nuclear fraction; RPPH1, RN7SL1 and DANCR were found in cytosolic compartments and H19 and TUG1 in ribosomal fractions. Although high levels of TUG1 occur in nucleus, but authors have found appreciable levels in ribosomal fractions also. This diverse localization of various lncRNAs in different sub-cellular compartments implies that an extensive array of functions is associated with lncRNAs than is known so far. So in overall for the functional characterization of these individual lncRNAs the data presented in this very study can be of priceless use.

Reference: Extensive localization of long noncoding RNAs to the cytosol and mono- and polyribosomal complexes. Sebastiaan van Heesch, Maarten van Iterson, Jetse Jacobi, Sander Boymans, Paul B Essers, Ewart de Bruijn, Wensi Hao, Alyson W MacInnes, Edwin Cuppen and Marieke Simonis. Genome Biology 2014, 15:R6  doi:10.1186/gb-2014-15-1-r6