Friday, June 25, 2010

Role of Peroxisomes in Dengue response

The recent paper in PLoS NTD caught my attention since Pex14 and Pex13 are reported to be among 273 “Common Dengue Response genes” which are up-regulated in Dengue virus infections. So I thought of having a closer look into the microarray data and I fished out peroxisomal genes that are up or down-regulated in Dengue infection.

Citation -
Loke P, Hammond SN, Leung JM, Kim CC, Batra S, et al. (2010)
PLoS Negl Trop Dis 4(6): e710. doi:10.1371/journal.pntd.0000710

(Kindly note that authors report vast microarray data, but I am discussing only about peroxisome specific genes in this post. Please consult the original paper for other details and proper context)

Dengue Virus (DENV) is single stranded RNA virus transmitted to human by mosquito Aedes aegypti. Dengue viral infection elicits wide spectrum of clinical manifestations. The authors performed transcriptional profiling of patient samples and found that there is distinct transcriptional profile associated with each clinical outcome.

*  DF    - Dengue Fever
*  DHF - Dengue Hemorrhagic Fever
*  DSS  - Dengue Shock Syndrome

Peroxins/Peroxisomal proteins significantly up/down regulated in Dengue infections

It should be noted that Pxmp2, the peroxisomal integral membrane protein is up-regulated in all Dengue clinical outcomes. So I will discuss about Pxmp2 in detail.

Confusion between PMP22 and Pxmp2

Pxmp2 is a peroxisomal multipass integral membrane protein which is highly expressed in tissues like liver, heart and kidney. Another peroxisomal membrane protein PMP70 is now known as Pxmp1. Since size of Pxmp2 is 22kD, it was also known as PMP22. But currently, PMP22 is official name of Peripheral Myelin Protein which is totally unrelated to Pxmp2.

Pxmp2 carries two distinct peroxisomal targeting signals, one in each N-terminal and C-terminal domain, both of which interact with Pex19 and get sorted to peroxisome membrane. Pxmp2 is the first peroxisomal protein experimentally shown to be a channel forming protein by Hiltunen group (Rokka et al). It is speculated by the authors that since Pxmp2 channel is open for longer times, it might allow non-specific small molecule transport.

Figure 1 from the paper of Rokka et al. (Compare the electron density between two)

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