Why do we remember so many details of our experiences even when it is unclear if we will actually ever need them?
In a new preprint, @marcelomattar.bsky.social and I asked whether this property is adaptive, because what will be relevant in the future often (usually?!) isn’t apparent.
Oh now that is cool!
Spiking activity in oyster fungi
www.nature.com/articles/s41...
![Top: MRAP2 facilitates the import of MC4R into cilia. Representative images of IMCD3-[MC4R3NG] (top row) or IMCD3-[MRAP23FLAG;MC4R3NG] (bottom row). Serum-starved cells were treated for 24 h with either HS014, AgRP, or vehicle, then fixed and stained for acetylated tubulin (acTub, magenta) and DNA (cyan). MC4R3NG was visualized through the intrinsic fluorescence of NG (yellow). The yellow and magenta channels are shifted to facilitate visualization of ciliary signals in the insets. Scale bars: 5 μm (main panel) and 1 μm (inset). Bottom: General and MC4R-specific models of regulated trafficking. Most ciliary GPCRs undergo exit once activated by their agonist. In the case of MC4R, exit is spontaneous in the absence of ligand and only in the presence of an inverse agonist does MC4R exit become interrupted. In both models, β-arrestin senses the activated state of the GPCR (agonist bound for most GPCRs, ligand free or agonist-bound for MC4R) and recruits the ubiquitination machinery to the activated GPCR. Unique to MC4R is that the receptor constitutively couples to β-arrestin. Once ubiquitinated, ciliary GPCRs are committed for retrieval back into the cell via TOM1L2 (dark purple) which endows the BBSome (pink) with the ability to recognize ubiquitin chains and move ubiquitinated proteins out of cilia.](https://cdn.bsky.app/img/feed_thumbnail/plain/did:plc:5522ztebtekoor5efelihqhb/bafkreie3fepqrfc4e5tmfeb2jwquezqlsg5gosrgqe2qlaycqyxs5gntfu)
Top: MRAP2 facilitates the import of MC4R into cilia. Representative images of IMCD3-[MC4R3NG] (top row) or IMCD3-[MRAP23FLAG;MC4R3NG] (bottom row). Serum-starved cells were treated for 24 h with either HS014, AgRP, or vehicle, then fixed and stained for acetylated tubulin (acTub, magenta) and DNA (cyan). MC4R3NG was visualized through the intrinsic fluorescence of NG (yellow). The yellow and magenta channels are shifted to facilitate visualization of ciliary signals in the insets. Scale bars: 5 μm (main panel) and 1 μm (inset). Bottom: General and MC4R-specific models of regulated trafficking. Most ciliary GPCRs undergo exit once activated by their agonist. In the case of MC4R, exit is spontaneous in the absence of ligand and only in the presence of an inverse agonist does MC4R exit become interrupted. In both models, β-arrestin senses the activated state of the GPCR (agonist bound for most GPCRs, ligand free or agonist-bound for MC4R) and recruits the ubiquitination machinery to the activated GPCR. Unique to MC4R is that the receptor constitutively couples to β-arrestin. Once ubiquitinated, ciliary GPCRs are committed for retrieval back into the cell via TOM1L2 (dark purple) which endows the BBSome (pink) with the ability to recognize ubiquitin chains and move ubiquitinated proteins out of cilia.
MC4R regulates #BodyWeight at hypothalamic neuronal #cilia, but its levels are normally v low. @nachury.bsky.social &co show that MC4R accumulation is prevented via continuous ubiquitin- & β-arrestin-dependent exit from cilia, unless MC4R is inhibited by AgRP 🧪 @plosbiology.org plos.io/40MWUUz
