American Society for Cell Biology Meeting

Denver, CO: December 3^rd (Saturday) – December 7^th (Wednesday)

REFERENCE:  Science (2011) 334 pgs 1046 - 1051

                This Saturday marks the beginning of the annual ASCB meeting in Denver, CO.  The event will feature over 3000 scientific poster presentations as well as 100 scientific sessions.  Principal Investigators, post doctoral associates and graduate students from all over the world will descend on Denver to discuss science (and ski) starting this weekend.

                As a preview to this event, Science magazine published a five article series discussing some of the most pressing questions currently facing cell biologists.  They include…

Do lipid rafts exist?  This is a contentious topic, but important to understand.  The plasma membrane is the first line of defense for a cell and acts as a gate keeper to all the comings and goings.  Understanding how it works is essential.

How does a cell know its size?  Many different kinds of cells exist but all of them stay within a certain size.  Certain proteins have been identified in yeast and bacteria that are involved in cells “sensing” their size but more work needs to be done.

How does a cell position its proteins?  Some cells make upwards of 10,000 proteins.  Positioning all of them so that they are in the proper places to perform their functions efficiently is a monumental task.  Proteins carry targeting sequences that place them in different organelles, but new research suggests that mRNAs may also be playing a role.

How do hungry cells start eating themselves? Autophagy is becoming a hot topic!

Does a gene’s location in the nucleus matter? Nuclear organization is important to cell function.  In fact, in cancer and other diseases, the nucleus is reorganized.  Researchers are trying to understand why the cell likes its proteins and RNA in certain places relative to its chromosomes.

I highly recommend reading them.  The articles are short and already written in a summary format.  I don’t want to write a redux of a redux on this blog because that is ridiculous.  Instead, I implore you to pick up a November 25^th copy of Science magazine and read pages 1046 – 1051!

Prions

Weissmann et al. “Prions on the move.” (2011) EMBO Reports 12(11) pgs 1109 – 1117.

             

                Prions are the infectious agents responsible for Creutzfeldt-Jakob disease, scrapie and bovine spongiform encephalopathy.  PrP^C is a 208 amino acid protein with two potential glycosylation sites.  Typically, it is found GPI-anchored to the plasma membrane outer surface.  PrP^SC is an aggregate of misfolded PrP molecules.  The aggregate recruits properly folded PrP to promote sequestration, protein misfolding and aggregate growth.

                A recent review by Browning and colleagues explores the recent literature to explain the leading theories on “barrier to transmission” and how prions can adapt to new environments.

                Consider a situation where the donor PrP is different in amino acid sequence from the recipient PrP.  Recipient PrP may have trouble joining the donor PrP aggregate for two reasons.  One, the differences in amino acid sequence may not allow the recipient PrP to adopt the necessary conformation needed for stable addition.  However, even when the PrP sequence is exactly the same, recipient PrP may still have problems, leading to the idea that different cellular environments and perhaps other proteins are involved in aggregate growth.

                An interesting study took 22L prions that could chronically infect PK1 cells in the presence of R33 cells and swainsonine.  Swainsonine is a small molecule that causes misglycosylation of proteins.  After forty population doublings, the prion population had become R33-incompetent and was sensitive to swainsonine.  When these new prions were placed back in the environment of the brain, the population changed back to being R33-competent and swainsonine insensitive.  

                The authors offer an excellent summation of these findings: “…a prion strain is a quasi-species, consisting of a major component and many variants, which are constantly being generated and selected against in a particular environment, as described earlier for RNA viruses and retroviruses.”  Comparing the adaptability of prions, a misfolded protein, to that of viruses, which bear genetic material and can respond to cellular changes with more plasticity, is fascinating.  The field strongly feels the changes in properties are most likely due to change in PrP^SC conformation.  

                Unfortunately, it also means that prions can develop drug resistance.  For this reason, many feel the best way to stop aggregate formation is to stop PrP synthesis or accelerate its turnover.  This idea has merit since PrP depletion in mice does not lead to devastating side effects.  However, the authors do end on the downer by saying that “no effective therapy is on the horizon.”