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Memory Molecules Move

March 6, 2014

At the recent Boskone, a panel discussed why some of us are writing science fiction on Earth, rather than some distant star. My reason is that science has multiple frontiers, in many dimensions–such as the interior of living cells. Now, scientists at Albert Einstein can watch the molecules of memory move within a neuron. The Science report is here.

Postdoc Hye Yoon Park worked with Robert Singer (and a long list of collaborators, as always) to construct a mouse in which the memory molecules can be seen. The molecules (moving white dots–click video) are messenger RNA, the RNA copies of an archival DNA gene. The gene expresses the messenger RNA to specify beta-actin protein, synthesized by a ribosome. But the amount of mRNA is what determines how much beta-actin gets made. And where the RNA goes–there goes the protein. Beta-actin transport within a neuron (nerve cell) is associated with extending the dendrites, the spine-like projections that connect to other neurons and help form memories.

So how did Park make this special mouse with fluorescence-tagged mRNA?

memorymouse

As usual, she used that Nobel-winning protein, GFP (Green Fluorescent Protein, originally made by a jellyfish, now made by bacteria, mice, plants, in every scientist’s lab). First, the MCP mouse (light green) was made “transgenic” by inserting the gene specifying GFP into its genome. This was done using a lentiviral vector–the research equivalent of those life-saving gene therapy vectors made from HIV (the AIDS virus, remember). The vector is constructed to contain the gene encoding GFP, located between two lentiviral integration sites. But in this case the GFP gene is “fused” (its sequence attached to) the sequence for another protein, MCP. MCP is the coat protein of a bacteriophage (a kind of virus that infects bacteria). If this starts to sound mixed up, remember this is the postmodern Franken-gene era; every useful gene gets constructed out of bits and pieces from wherever.

Now a different mouse also gets constructed (the gray one above) in which the mRNA for beta actin has some extra sequence fused, called the MBS sequence. The MBS sequence of RNA specifically binds to MCP protein.

Next–unbelievable though it may sound–the next step is actually to cross breed the two lucky mice (yes, they get to have fun the time-honored traditional way). I guess in vitro IVF could do as well, but many mouse breeders actually still do the old fashioned thing, usually picking up a male mice by the tail from one bin, and a female mouse by the tail from another bin. As a result (aside) many lab-bred mouse strains evolve low vision, because the ones that don’t see the hand coming for the tail get to breed.

Anyway, the result is the (dark green) mouse, whose neurons express both the GFP-fused MCP phage coat protein and the MBS tagged mRNA sequence that binds the fluorescent GFP-MCP protein. So wherever beta-actin mRNA goes, the GFP is sure to bind and light up fluorescent. Watch the cool video. Where the mRNA goes, and how it stores memories, is a story for another day.

2 Comments
  1. SFreader permalink
    March 9, 2014 11:42 am

    Do ‘we’ know how many/which genes are expressed in any given cell?
    What impact, if any, does using GFP have on a cell, its metabolism, types of reactions occurring within that cell?

    • March 9, 2014 1:55 pm

      This particular assay involves only one gene, encoding beta actin protein. As for the effect of GFP on the cell, the researchers don’t fully know. They have to argue that the live mouse behaves normally, so the GFP effects are not impairing it. Look at it this way: If the transgenic mouse is functional and healthy, compared to non-GFP mice, then the GFP may be considered a normal part of that mouse’s body.

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