Rab5 Knockdown In Vivo

This paper from the Zerial Laboratory describes a study in which the three mammalian isoforms of Rab5 are reduced in whole livers or cultured hepatocytes by a lipid nanoparticle mediated knockdown treatment. They then analyse images from these cells and liver sections and determine that there are reduced early endosomes, late endosomes and lysosomes in cells depleted of Rab5.

They also identify two functional defects in these tissues; reduced LDL uptake and impaired apical polarity of the hepatocytes. They also generate a simplified model of Rab5/early endosomal dynamics and suggest a role for Rab5 in vesicle fission as well as fusion. Although this model fits the available data quite well, it ignores several other key components of endosomal formation and maturation.

The authors also present the curious finding that while Rab5 depletion reduces both LDL uptake and endosome numbers, dynamin depletion only affects LDL uptake but not the number of endosomes. One possible explanation for this defect is that they quantify the presence of endosomes in this assay largely by EEA1 puncta. Since EEA1 is a Rab5 effector, it is possible that in the Rab5 depleted cells there is still a population of early endosomes, but that these are not detected by EEA1 staining.

Together this study presents a convincing picture for the role of Rab5 in endosomal dynamics, and highlight the important role of Rab5 in both endocytic pathways and in the establishment of polarity in vivo.

Citation

Zeigerer A, Gilleron J, Bogorad RL, Marsico G, Nonaka H, Seifert S, Epstein-Barash H, Kuchimanchi S, Peng CG, Ruda VM, Del Conte-Zerial P, Hengstler JG, Kalaidzidis Y, Koteliansky V, & Zerial M (2012). Rab5 is necessary for the biogenesis of the endolysosomal system in vivo. Nature, 485 (7399), 465-70 PMID: 22622570

Disclosure: I have received constructs and yeast strains from the Zerial laboratory in the past.



Rab5 Knockdown In Vivo by Dave Bridges is licensed under a Creative Commons Attribution 3.0 Unported License.

Why Isn't There Anonymous Post-Publication Peer Review

If pre-publication review is anonymous, and it almost always is why isnt there anonymous post-publication peer review? If there is a benefit to anonymous review, then isn't it odd that the Faculty of 1000 and most journals commenting/letter to editor mechanisms require the submitter to provide a real name and appointment. Would post-publication review of articles suck less if it were anonymous?

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Based on the twitter meme #whydoiblog. This is a good question, seeing as I do this infrequently and without a ton of focus. I guess I'd say to get something off my chest that I think other people might want to hear. I aspire towards being able to talk about research in a more public and open way, but until I am independent that is unfair to people who might not want to operate that way. Until then I'll continue to use this as a sporadic forum for me to speak out to the ether.

Why Blog by Dave Bridges is licensed under a Creative Commons Attribution 3.0 Unported License.