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We are analyzing https://www.biorxiv.org/content/10.1101/2023.07.13.548866v3.

Title:
Sequential replacement of PSD95 subunits in postsynaptic supercomplexes is slowest in the cortex | bioRxiv
Description:
The concept that dimeric protein complexes in synapses can sequentially replace their subunits has been a cornerstone of Francis Crick’s 1984 hypothesis, explaining how long-term memories could be maintained in the face of short protein lifetimes. However, it is unknown whether the subunits of protein complexes that mediate memory are sequentially replaced in the brain and if this process is linked to protein lifetime. We address these issues by focusing on supercomplexes assembled by the abundant postsynaptic scaffolding protein PSD95, which plays a crucial role in memory. We used single-molecule detection, super-resolution microscopy and MINFLUX to probe the molecular composition of PSD95 supercomplexes in mice carrying genetically encoded HaloTags, eGFP and mEos2. We found a population of PSD95-containing supercomplexes comprised of two copies of PSD95, with a dominant 12.7 nm separation. Time-stamping of PSD95 subunits in vivo revealed that each PSD95 subunit was sequentially replaced over days and weeks. Comparison of brain regions showed subunit replacement was slowest in the cortex, where PSD95 protein lifetime is longest. Our findings reveal that protein supercomplexes within the postsynaptic density can be maintained by gradual replacement of individual subunits providing a mechanism for stable maintenance of their organization. Moreover, we extend Crick’s model by suggesting that synapses with slow subunit replacement of protein supercomplexes and long protein lifetimes are specialized for long-term memory storage and that these synapses are highly enriched in superficial layers of the cortex where long-term memories are stored. ### Competing Interest Statement The authors have declared no competing interest. * SR : super-resolution PALM : photoactivation localization microscopy MINFLUX : MINimal photon FLUXes TIRF : total internal reflection fluorescence GFP : green fluorescent protein LPL : long protein lifetime SPL : short protein lifetime
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12 years and 2 months (reg. 2013-04-08).

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💥 Very Strong Traffic: 200k - 500k visitors per month


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How Does Biorxiv.org Make Money? {💸}

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Keywords {🔍}

protein, biology, psd, supercomplexes, subunits, replacement, lifetime, medrxiv, subject, reviews, clinical, preprint, postsynaptic, cortex, synapses, sequentially, longterm, memory, subunit, biorxiv, university, trials, epidemiology, search, results, slowest, pdf, abstract, complexes, cricks, memories, maintained, short, lifetimes, replaced, brain, superresolution, microscopy, minflux, molecular, long, competing, interest, authors, copyright, license, institute, technology, cancer, neuroscience,

Topics {✒️}

super-resolution microscopy short protein lifetimes psd95 protein lifetime protein lifetime epidemiology subject categories long protein lifetimes clinical trials long-term memory storage copyright holder molecular composition minflux dimeric protein complexes long-term memories biorxiv subject category genetics microbiology reviews epidemiology papers protein complexes protein supercomplexes author/funder keyword advanced search health-related information slow subunit replacement lorena mendive-tapia single-molecule detection generous financial support chan zuckerberg initiative imperial college london vrije universiteit amsterdam articles animal behavior competing interest statement context preprint sequential replacement individual subunits providing cortex katie morris psd95 subunit gradual replacement postsynaptic supercomplexes postsynaptic density competing interest mediate memory psd95 supercomplexes psd95 subunits results follow edita bulovaite takeshi kaizuka sebastian schnorrenberg candace adams sequentially replace

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