Limits...
The proteins behind the persistence of memory.

Robinson R - PLoS Biol. (2014)

View Article: PubMed Central - PubMed

Affiliation: Freelance Science Writer, Sherborn, Massachusetts, United States of America.

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The CPEB protein at work in the fruit fly is Orb2, which occurs in two isoforms: Orb2A and Orb2B... Orb2A, by far the rarer of the two, has a prion-like domain, so the authors began by searching for Orb2A binding partners... They found quite a few, but one in particular, called Tob, intrigued them, in part because it also appeared to regulate Orb2A levels, which suggested Tob might stabilize the usually labile Orb2A... Indeed, increasing Tob almost doubled the half-life of Orb2A and reducing it depleted Orb2A (neither action had an effect on Orb2B)... Furthermore, activation of fly neurons enhanced the association of Tob and Orb2A, suggesting their linkage plays a role in response to synaptic activity... If loss of phosphate destabilizes Orb2A, and if Tob's role is to stabilize Orb2A and enhance its oligomerization, one way Tob might do so would be to promote addition of phosphates to Orb2A... The authors found that LimK, a kinase acting on Tob, also phosphorylated Orb2A when Orb2A was linked to Tob... That phosphorylation was also critical to the oligomerization process; when LimK was present but inactivated, there was no increase in oligomerization in response to neuronal stimulation... The model the authors propose based on these results posits that in the unstimulated synapse, PPA destabilizes newly synthesized Orb2A and prevents oligomerization... This triggers oligomerization, including of the more abundant Orb2B... The presence of Orb2 oligomers maintains the translational changes underlying the change in synaptic strength... Much remains unknown about this dynamic system, including whether and how Tob and LimK may be involved in regulating the Orb2-dependent translation that follows oligomerization... But with the identification of this important regulatory system, it is likely that a more detailed understanding of post-stimulation memory maintenance will emerge relatively quickly... doi:10.1371/journal.pbio.1001786

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Tob (green) binds and increases the amount of monomeric Orb2A (red), which facilitates conformational change and oligomerization of Orb2 (yellow).Image Credit: Nicolle Rager Fuller, Sayo-Art.
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pbio-1001787-g001: Tob (green) binds and increases the amount of monomeric Orb2A (red), which facilitates conformational change and oligomerization of Orb2 (yellow).Image Credit: Nicolle Rager Fuller, Sayo-Art.


The proteins behind the persistence of memory.

Robinson R - PLoS Biol. (2014)

Tob (green) binds and increases the amount of monomeric Orb2A (red), which facilitates conformational change and oligomerization of Orb2 (yellow).Image Credit: Nicolle Rager Fuller, Sayo-Art.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921103&req=5

pbio-1001787-g001: Tob (green) binds and increases the amount of monomeric Orb2A (red), which facilitates conformational change and oligomerization of Orb2 (yellow).Image Credit: Nicolle Rager Fuller, Sayo-Art.

View Article: PubMed Central - PubMed

Affiliation: Freelance Science Writer, Sherborn, Massachusetts, United States of America.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The CPEB protein at work in the fruit fly is Orb2, which occurs in two isoforms: Orb2A and Orb2B... Orb2A, by far the rarer of the two, has a prion-like domain, so the authors began by searching for Orb2A binding partners... They found quite a few, but one in particular, called Tob, intrigued them, in part because it also appeared to regulate Orb2A levels, which suggested Tob might stabilize the usually labile Orb2A... Indeed, increasing Tob almost doubled the half-life of Orb2A and reducing it depleted Orb2A (neither action had an effect on Orb2B)... Furthermore, activation of fly neurons enhanced the association of Tob and Orb2A, suggesting their linkage plays a role in response to synaptic activity... If loss of phosphate destabilizes Orb2A, and if Tob's role is to stabilize Orb2A and enhance its oligomerization, one way Tob might do so would be to promote addition of phosphates to Orb2A... The authors found that LimK, a kinase acting on Tob, also phosphorylated Orb2A when Orb2A was linked to Tob... That phosphorylation was also critical to the oligomerization process; when LimK was present but inactivated, there was no increase in oligomerization in response to neuronal stimulation... The model the authors propose based on these results posits that in the unstimulated synapse, PPA destabilizes newly synthesized Orb2A and prevents oligomerization... This triggers oligomerization, including of the more abundant Orb2B... The presence of Orb2 oligomers maintains the translational changes underlying the change in synaptic strength... Much remains unknown about this dynamic system, including whether and how Tob and LimK may be involved in regulating the Orb2-dependent translation that follows oligomerization... But with the identification of this important regulatory system, it is likely that a more detailed understanding of post-stimulation memory maintenance will emerge relatively quickly... doi:10.1371/journal.pbio.1001786

Show MeSH