A conserved mechanism for the retrieval of polyubiquitinated proteins from cilia The temporospatial distribution of proteins within cilia is regulated by intraflagellar transport (IFT), wherein molecular trains shuttle between the cell body and cilium. Defects in this process impair various signal-transduction pathways and cause ciliopathies. Although K63-linked ubiquitination appears to trigger protein export from cilia, the mechanisms coupling polyubiquitinated proteins to IFT remain unclear. Using a multidisciplinary approach, we demonstrate that a complex of CFAP36, a conserved ciliary protein of previously unknown function, and ARL3, a GTPase involved in ciliary import, binds polyubiquitinated proteins and links them to retrograde IFT trains. CFAP36 uses a coincidence detection mechanism to simultaneously bind two IFT subunits accessible only in retrograde trains. Depleting CFAP36 accumulates K63-linked ubiquitin in cilia and disrupts Hedgehog signaling, a pathway reliant on the retrieval of ubiquitinated receptors. These findings advance our understanding of ubiquitin-mediated protein transport and ciliary homeostasis, and demonstrate how structural changes in IFT trains achieve cargo selectivity. ### Competing Interest Statement The authors have declared no competing interest. Sara Elizabeth O'Brien Trust Postdoctoral Fellowship awarded through the Charles A. King Trust Postdoctoral Research Fellowship Program, , 8460873-01 Richard and Susan Smith Family Foundation, https://ror.org/05j95n956, National Institute of General Medical Sciences (NIGMS), , R01GM141109, R01GM143183

How do cells keep their cilia “clean” and functional? Our new study uncovers a conserved mechanism for retrieving polyubiquitinated proteins from #cilia – a process essential for cellular signaling and health. #cellbiology #ciliopathy #ubiquitin #IFT 🧵👇 1/n

Well done, Sven! It’s in my to-read list for the week!

'Ubiquitin Lysine-Linkages' from the review 'Ubiquitin: a structural perspective' in Molecular Cell

New to #ubiquitin? Been with it for a while? Either way this review may be for you 🤩

Excited to share our review article in @molcell.bsky.social, diving deep into everything #ubiquitin
Read here 👉: kwnsfk27.r.eu-west-1.awstrack.me/L0/https:%2F...

@cellpress.bsky.social
@wehi-research.bsky.social

Nikita Sergejevs

Read more about this research in our ‘First person’ interview with Nikita Sergejevs: journals.biologists.com/jcs/article/...

Proposed model of CYP51A1 recognition by SPP. In cells, the lanosterol demethylase CYP51A1 can exist in two distinct conformations, with only one conformation being recognized for membrane protein quality control. The early recognition event by SPP consists of an N-terminal cleavage within the AH of the substrate. This generates a truncated version of CYP51A1 that is subsequently recognized by the RNF185–MBRL E3 ubiquitin ligase complex, extracted from the ER membrane and degraded by the cytosolic proteasomes. APH, amphipathic helix.

Nikita Sergejevs, Pedro Carvalho and colleagues find that that the intramembrane protease SPP conducts topology surveillance of CYP51A1 by initiating quality control of incorrectly inserted molecules.
Highlight: journals.biologists.com/jcs/article/...
Article: journals.biologists.com/jcs/article/...

Congratulations! Lucky us in Dundee as we will get to hear your exciting research, past and present when you deliver the Adam Neville Lecture tomorrow. I am very much looking forward to it!

Graphic Abstract for "Yeast Knowledge Graphs Database for Exploring Saccharomyces cerevisiae and Schizosaccharomyces pombe"

🚨 Our latest study, "Yeast Knowledge Graphs Database for Exploring Saccharomyces cerevisiae and Schizosaccharomyces pombe," has just been deposited in @biorxivpreprint.bsky.social ! We’re thrilled to share our work with the world! #KnowledgeGraphs
www.biorxiv.org/content/10.1101/2024.12.04.626523v1

Waves of new BlueSky arrivals in last few days!

I’ve been tracking starter packs relevant to molecular/mechanistic/genetic/cellular…etc biology

Hope it’s helpful but warning: now a v long thread!

Probably the last time I can do this...

If you are interested in doing cutting-edge molecular #neurobiology research, I can highly recommend the opportunity to work with @adamgrieve.bsky.social, whom not only will ensure you an exciting scientific journey, but will also be a great mentor, guiding you through the ups and downs of a #PhD.

Amazing PhD opportunity to join an exciting new lab at Bristol Biochemistry - send your best students in Ferdos’ direction!

This study has it all! A truly structure-to-function study on two #deubiquitinases that were thought to be pseudoenzymes and providing insights into disease mutations. Congratulations to @gallantkai.bsky.social, Kim and the team!

Since I read about AKIRIN2 in 2021 in their earlier paper in Nature, I have always been fascinated by this protein. This follow-up preprint is aimed at unraveling the mechanistic aspects of its functions! Just excited at the fact that we have so much more to learn about the world of #proteostasis!

It was a treat to hear this story when @micharapelab.bsky.social visited University of Dundee and continuation of the story at the EMBO #ubiquitin and #ubiquitin-like proteins meeting in Cavtat, a couple months ago! Very elegant and informative mechanistic and functional works on #stresssignalling!

Reactive oxygen species control protein degradation at the mitochondrial import gate This work identifies reactive oxygen species released by the electron transport chain as sentinel molecules that regulate localized protein degradation at mitochondrial TOM complexes, a mechanism that controls mitochondrial protein import and adjusts the abundance of the electron transport chain to cellular needs.

Excited to reveal specific reactive oxygen species as sentinel molecules that control localized protein degradation at #mitochondria to adjust electron transport chain abundance, with many implications for the role of ROS in development and disease.

www.cell.com/molecular-ce...

PITHD1: An Endogenous Inhibitor of the 26S Proteasome During Cellular Dormancy Cellular dormancy represents a state of regulated growth arrest essential for diverse biological processes, from reproduction to cancer progression. While mechanisms controlling protein synthesis in d...

The second of our two new preprints addresses the question of how proteasomes can be kept dormant for instance in oocytes. This study was spearheaded by first author Sascha Amann. biorxiv.org/cgi/content/... (1/6)🧵

‘Dark proteome’ survey reveals thousands of new human genes Database confirms that overlooked segments of the genome code for a multitude of tiny proteins

A humbling reminder that we've only scratched the surface of life's complexity.
www.science.org/content/arti...

SAVE THE DATE 🗓️Ubiquitin & Friends Symposium: 8-9 May 2025 in Vienna!
Registration will open🔜 Keep an eye out for the announcement 👀
✨guest speaker lineup👇🧵 +talks from abstracts! Great chance for #ECRs to meet with peers & experts in a friendly setting!
🔗 www.protein-degradation.org/symposium/

Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12 The oxidative stress response is centered on the transcription factor NRF2 and protects cells from reactive oxygen species (ROS). While ROS inhibit the E3 ligase CUL3-KEAP1 to stabilize NRF2 and elici...

Excited to report our discovery of an important component of the oxidative stress response: the E3 ligase TRIP12. It acts as a chain elongation factor that amplifies CUL3-KEAP1 activity to drive NRF2 degradation as cells recover from stress.

www.biorxiv.org/content/10.1...

Figure 4. Position and type of fluorescent tag affect protein expression and P-body numbers in vivo.

The dark side of fluorescent protein tagging: the impact of protein tags on biomolecular condensation
www.biorxiv.org/content/10.1...

For people interested in chaperones, protein quality control, proteostasis and cellular homeostasis, here is the link of the webinars we (P. Goloubinoff, A. Barducci, N. Nillegoda and I) hosted during the COVID pandemics. A lot of material!

tinyurl.com/27y5wpzy

Hello! As a new user, I thought I would introduce myself. I am a postdoc in the lab of @kulathu.bsky.social at MRC-PPU, Dundee, UK. Fascinated by #molecularchaperones and #proteinqualitycontrol. Find me on pubmed pubmed.ncbi.nlm.nih.gov?term=Logesva... or here scholar.google.com/citations?us...

Hi Dorien, Loges here from Dundee, UK. Postdoc, a molecular cell biologist. I would really like to be added to this group. Thank you!

We are still considering postdoc candidates for the post advertised below. A 2-year contract beginning in 2025 to work on protein SUMO E3 ligases and the nucleosome.