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Peter Cullen

@peterjcullen1.bsky.social

University Researcher, All things: Endosomes, Lysosomes, Retromer, Retriever, Sorting nexins, Commander, RABs, et al.

272 Followers  |  159 Following  |  9 Posts  |  Joined: 14.11.2024
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Posts by Peter Cullen (@peterjcullen1.bsky.social)

The GTPase activating protein Gyp6 binds Retromer and inactivates Rab7/Ypt7 to coordinate the formation of endosomal carriers The Retromer coat is conserved in all eukaryotes and is crucial for the correct intracellular sorting of many transmembrane receptors and lysosomal hydrolases. Retromer is an effector of the late endosomal small GTPase RAB7 and is also implicated in its inactivation required for proper endosomal maturation. Here, we explore the role of controlled GTP hydrolysis by the RAB7 ortholog Ypt7 in the formation of Retromer-coated membrane carriers in yeast. Proximity labelling and genetic ablation identify the GTPase Activating Protein (GAP) Gyp6 as a critical regulator of Ypt7 activity in the context or Retromer. Structural studies show that Retromer recruits Gyp6 through its Vps29 subunit, which recognises a specific PL motif and a secondary binding site in the C-terminal domain of Gyp6. This interaction does not occur with other yeast GAPs. Ablation of the Gyp6-Retromer interface or the catalytic activity of Gyp6 leads to the accumulation of tubular structures on endo-lysosomal compartments and to increased association of Ypt7 with Retromer and its cargo Vps10. These results support a model in which Gyp6 controls the switch from Ypt7-dependent Retromer coat assembly and cargo collection to the departure of the carrier through membrane fission and uncoating. ### Competing Interest Statement The authors have declared no competing interest. National Health and Medical Research Council, https://ror.org/011kf5r70, APP2016410 Swiss National Science Foundation, https://ror.org/00yjd3n13, 31003A_179306, 310030_204713, 10.006.083

Do you want to know more about how Retromer regulates Rab7 activity in yeast? Of course you do. Check out the new collaboration with Andreas Mayer with work led by Catarina Alves and Kevin Chen.

28.01.2026 01:25 β€” πŸ‘ 20    πŸ” 10    πŸ’¬ 0    πŸ“Œ 0
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Happy to share that I passed my PhD viva on 21st Jan 2026 πŸŽ“πŸŽ‰

A great 4-hour discussion with Sharon A. Tooze & Sylvie UrbΓ©, chaired by Jon Lane. Huge thanks to my supervisor Pete Cullen, my lab mates, collaborators, and my funder EndoConnect for all the support along the way.

27.01.2026 01:54 β€” πŸ‘ 3    πŸ” 1    πŸ’¬ 0    πŸ“Œ 0
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Seen on way back to London from ASCB. As Jez Carlton said β€œif rudder falls off will it regenerate”. Have a good flight home everyone after another great meeting…… long may ASCB continue

10.12.2025 19:24 β€” πŸ‘ 23    πŸ” 2    πŸ’¬ 1    πŸ“Œ 0

30-years ago today I started my lab in Bristol Biochemistry, it's been a fun ride! Massive thanks to all those past and present lab members and academic colleagues for their friendship, advice and support.

01.12.2025 07:41 β€” πŸ‘ 14    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0

Congrats Steve, a paper full of interesting data (especially, in my opinion, Fig. 6). Interesting that so many proteins associated with binding the 'early' endosome PI(3)P are labelled by the 'late' endosome RAB7. Also, the clear segregation of Retromer from ESCPE-1.

29.11.2025 22:15 β€” πŸ‘ 0    πŸ” 0    πŸ’¬ 1    πŸ“Œ 0
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A proximity map of RAB GTPases delineates roles for RAB14 in EARP complex and UHRF1BP1 endosomal recruitments Communications Biology - Proximity labeling proteomics of RAB GTPases identifies an array of neighboring RAB proteins. Functional validation studies reveal links between RAB25 and DENND6A, or...

It is a nice way to end the week: our improved RAB GTPase BioID map now online! www.nature.com/articles/s42... We hope it will be useful to the community, and we're happy to share any reagents!

28.11.2025 16:27 β€” πŸ‘ 35    πŸ” 10    πŸ’¬ 5    πŸ“Œ 1
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Add our first pre-print to your reading list?

Using AF2 and MD, we've characterised structures and conformational ensembles of human rhomboid proteases - and revealed some surprises along the way. Feel v.lucky to work alongside Bryony & @robincorey.bsky.social!

Please share: tinyurl.com/3h8r7f5y

25.11.2025 09:57 β€” πŸ‘ 12    πŸ” 5    πŸ’¬ 1    πŸ“Œ 2
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Excited to announce, the 93rd Biochemical Society Harden Conference will be on "Endosomal-lysosomal network dysfunction in neurodegeneration". Come and join us in early September on the beautiful south coast of England. Lots of speaker slots available from submitted abstracts!

20.11.2025 16:37 β€” πŸ‘ 3    πŸ” 1    πŸ’¬ 0    πŸ“Œ 2
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Identification of a RAB32-LRMDA-Commander membrane trafficking complex reveals the molecular mechanism of human oculocutaneous albinism type 7 Nature Communications - Membrane trafficking is essential for organelle biogenesis. Here, the authors discover an alternative assembly of the Commander trafficking complex and show its role in...

Latest endosomal publication with @brettcollins.bsky.social: Rebeka Butkovic's beautiful work identifying a new Commander assembly, the RAB32-LRMDA-Commander, and its role in melanosome biogenesis. Reveals molecular mechanism of human oculocutaneous albinism type 7. www.nature.com/articles/s41...

02.10.2025 10:30 β€” πŸ‘ 14    πŸ” 5    πŸ’¬ 0    πŸ“Œ 0

Structures of EHD2 filaments on curved membranes provide a model for caveolar neck stabilization https://www.biorxiv.org/content/10.1101/2025.06.05.658037v1

07.06.2025 13:17 β€” πŸ‘ 2    πŸ” 2    πŸ’¬ 0    πŸ“Œ 0

Swifts have today arrived over the house. Summer’s here!!

03.05.2025 13:48 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0

That looks fun! Hobbies?

03.05.2025 13:22 β€” πŸ‘ 0    πŸ” 0    πŸ’¬ 1    πŸ“Œ 0

Pleased to see Kevin's paper on the Retromer complex interaction with yeast Vps5 and Vps17 proteins now online!

16.04.2025 01:59 β€” πŸ‘ 28    πŸ” 8    πŸ’¬ 2    πŸ“Œ 0

Moving obituary of David Stephens, "in many ways, the perfect academic" journals.biologists.com/jcs/article/...

15.04.2025 15:33 β€” πŸ‘ 36    πŸ” 15    πŸ’¬ 0    πŸ“Œ 0
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Molecular mechanism for cargo-mediated initiation of kinesin-1 activation Kinesin-1 is a dynamic heterotetrameric assembly of two heavy and two light chains (KHC and KLC) that mediates microtubule-based intracellular transport of many different cargoes. The complex adopts a...

New preprint on kinesin inhibition and activation - collaborative effort across Bristol Biochem and Chemistry with Woolfson and Schaffizel labs and JJ Phillips in Exeter 1/2 www.biorxiv.org/content/10.1...

10.04.2025 13:02 β€” πŸ‘ 12    πŸ” 9    πŸ’¬ 1    πŸ“Œ 0
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Pls re-skeet! There's a postdoc job available to join us in Bristol! We're looking for a molecular cell biologist to help us investigate plasma membrane proteostasis in neurons. Apply here by 23 April: www.jobs.ac.uk/job/DMO097/r.... If interested, do contact me and check out grieve-lab.com! Thanks!

09.04.2025 15:42 β€” πŸ‘ 11    πŸ” 15    πŸ’¬ 1    πŸ“Œ 3

SNX-BAR proteins 5 and 6 are required for NCOA7-AS antiviral activity against influenza A virus https://www.biorxiv.org/content/10.1101/2025.04.01.646557v1

02.04.2025 04:17 β€” πŸ‘ 1    πŸ” 1    πŸ’¬ 0    πŸ“Œ 0
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Lysosomal acidification is key for cellular health, with impairment linked to aging & neurodegenerative diseases. Lin et al. identify USP45 as a negative regulator of autophagy, inhibiting V-ATPase localization to autolysosomes via Coronin 1B-actin modulation. rupress.org/jcb/article/...

11.03.2025 17:03 β€” πŸ‘ 13    πŸ” 2    πŸ’¬ 0    πŸ“Œ 0
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Coordination between ESCRT function and Rab conversion during endosome maturation | The EMBO Journal imageimageEarly endosome maturation requires Rab conversion and ESCRT function; however, how these processes are coordinated remains largely elusive. This study proposes that Rab conversion in both C....

Interested how events are coordinated during #endosome maturation? Check out our latest paper! Congrats Daniel, Samit and Jachen!
www.embopress.org/doi/full/10....

05.02.2025 15:53 β€” πŸ‘ 17    πŸ” 9    πŸ’¬ 0    πŸ“Œ 1
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Identification of a VPS29 isoform with restricted association to Retriever and Retromer accessory proteins through auto-inhibition. The endosomal-lysosomal network is a hub of organelles that orchestrate the dynamic sorting of hundreds of integral membrane proteins to maintain cellular homeostasis. VPS29 is a central conductor of ...

Two new lab manuscripts describing new insight into VPS29’s role in Retromer vs Retriever, and the identification of a non-classical Commander pathway in melanosome biogenesis. Both with @BrettCollins.bsky.social lab. www.biorxiv.org/content/10.1... and www.biorxiv.org/content/10.1...

04.02.2025 21:08 β€” πŸ‘ 25    πŸ” 9    πŸ’¬ 1    πŸ“Œ 0

Identification of a VPS29 isoform with restricted association to Retriever and Retromer accessory proteins through auto-inhibition. https://www.biorxiv.org/content/10.1101/2025.02.04.636264v1

04.02.2025 16:31 β€” πŸ‘ 1    πŸ” 1    πŸ’¬ 0    πŸ“Œ 0

Identification of a RAB32-LRMDA-Commander membrane trafficking complex reveals the molecular mechanism of human oculocutaneous albinism type 7 https://www.biorxiv.org/content/10.1101/2025.02.04.636395v1

04.02.2025 16:30 β€” πŸ‘ 2    πŸ” 1    πŸ’¬ 0    πŸ“Œ 0
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Newton International Fellowships | Royal Society This fellowship is for non-UK scientists who are at an early stage of their research career and wish to conduct research in the UK.

This is a fantastic route for international post docs to perform research in a UK lab. Bristol Biochemistry would be a great home, including our own endosomal-lysosomal lab. royalsociety.org/grants/newto...

14.01.2025 19:22 β€” πŸ‘ 1    πŸ” 1    πŸ’¬ 0    πŸ“Œ 0

And now onto @carlosantonplagaro.bsky.social from the Pete Cullen lab using BioID to understand the role of Rabs in fate determination in endosomal sorting - great work, Carlos! #UKMT2024

16.12.2024 15:05 β€” πŸ‘ 6    πŸ” 1    πŸ’¬ 0    πŸ“Œ 0

This is an great opportunity. Andrew, his science, and his team are amazing!

12.12.2024 15:30 β€” πŸ‘ 6    πŸ” 3    πŸ’¬ 0    πŸ“Œ 0

Endosome maturation is orchestrated by inside-out proton signaling through a Na+/H+ exchanger and pH-dependent Rab GTPase cycling https://www.biorxiv.org/content/10.1101/2024.12.09.627558v1

12.12.2024 15:32 β€” πŸ‘ 4    πŸ” 3    πŸ’¬ 0    πŸ“Œ 1

Finally my first author preprint at Cullen's lab is out! Amazing collaboration with Kevin and @brettcollins.bsky.social where, by using dedicated proximity proteomics, Biochemistry, crystallography and structural prediction, we show new aspects of human Retromer complex acting as hub for RAB GTPases

24.11.2024 18:37 β€” πŸ‘ 21    πŸ” 10    πŸ’¬ 2    πŸ“Œ 0
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Mapping the endosomal proximity proteome reveals Retromer as a hub for RAB GTPase regulation. Endosomal retrieval and recycling of integral cargo proteins is essential for cell, tissue and organism-level development and homeostasis and is orchestrated through a specialised retrieval sub-domain...

Our latest paper with @brettcollins.bsky.social is on bioRxiv. Fantastic work driven by Carlos Anton-Plagaro with unbelievable help from Kai-en Chen in Brett’s lab. A data-rich study with lots of new insight into Retromer, Retriever and potential AD/PD connections. www.biorxiv.org/content/10.1...

23.11.2024 13:07 β€” πŸ‘ 26    πŸ” 12    πŸ’¬ 0    πŸ“Œ 0

Very proud to be involved in this work with the Cullen lab. Carlos's proteomics is some of the nicest I've seen! Very carefully controlled proximity labelling reveals a number of novel Rab GTPase activators and regulatory proteins are directly associated with Retromer on the endosome.

23.11.2024 03:44 β€” πŸ‘ 22    πŸ” 9    πŸ’¬ 0    πŸ“Œ 0