Loon visited this morning

New to me. Painted trillium. Colton, NY

A pressure relief valve for #lysosomes. @laylanassar.bsky.social and @shawnferguson.bsky.social @yaleschoolofmed.bsky.social discuss Kim et al.’s new study (doi.org/10.1083/jcb....): rupress.org/jcb/article-...

Rainy night friend

@laylanassar.bsky.social & @shawnferguson.bsky.social @yaleschoolofmed.bsky.social discuss Kim et al.’s study (doi.org/10.1083/jcb....) showing that TMEM63A protects #lysosomes from rupture by acting as a pressure relief valve when membrane tension rises. rupress.org/jcb/article/...

It was a pleasure to work with @laylanassar.bsky.social to highlight this paper from @spencerfreeman.bsky.social and colleagues that shows how lysosomes can adapt in response to increased membrane tension

Rockefeller University Press@rupress.org · 3mo ago

@laylanassar.bsky.social & @shawnferguson.bsky.social @yaleschoolofmed.bsky.social discuss Kim et al.’s study in @jcb.org (doi.org/10.1083/jcb....) showing that TMEM63A protects #lysosomes from rupture by acting as a pressure relief valve when membrane tension rises. rupress.org/jcb/article/...

How do lysosomes rapidly adapt to membrane tension to avoid bursting? In this article, @laylanassar.bsky.social and I highlight discoveries from Angela Kim, Spencer Freeman and colleagues who show a role for TMEM63A, a mechanosensitive cation channel in protecting lysosomes doi.org/10.1083/jcb....

A pressure relief valve for lysosomes

Nassar and Ferguson discuss work from Kim et al. showing that TMEM63A protects lysosomes from rupture by acting as a pressure relief valve when membrane te

doi.org

Spotted salamander eggs in a vernal pool. Killingworth, CT

My friends are out and about again! Spring has officially sprung in Connecticut! 🦎

Last “ice neurons” of the year? Near Tupper Lake, NY last week

There are still spots available (get them while they last) for the 2026 Lysosomes and Endocytosis GRC (June 14-19, 2026). APPLY NOW if you are interested. Newcomers to the field or old friends, everyone is welcome! www.grc.org/lysosomes-an...

Vaults. They are cell biology's greatest puzzle! This preprint from Martin Beck's lab shows them docked on ER membranes with a ribosome inside. What on earth is going on there?? #CellBiology #WTFology www.biorxiv.org/content/10.6...

The vault associates with membranes in situ

The eukaryotic vault particle is a giant ribonucleoprotein complex that assembles into an iconic barrel-like cage. Its cellular function has remained elusive despite extensive characterization. Using ...

biorxiv.org

Congratulations to Amanda Bentley-DeSousa of the Ferguson lab for her paper being selected as one of JCB’s most impactful papers of 2025! @shawnferguson.bsky.social

Journal of Cell Biology@jcb.org · 8mo ago

Our annual collection highlights 13 of the year's most impactful papers that have garnered exceptional interest from our readership. Explore cutting-edge findings spanning the diverse spectrum of cell biology 👉 rupress.org/jcb/collecti... #CellBio2025 @ascbiology.bsky.social

I am excited to be co-organizing the 2026 Gordon Research Conference on Lysosomes & Endocytosis continuing a community tradition that has now spanned more than 50 years. www.grc.org/lysosomes-an...

New research led by Devin Clegg that defines how lysosome swelling and lysosome deacidification evoke distinct routes for LRRK2 activation: doi.org/10.1101/2025...

LRRK2 integrates Rab and GABARAP interactions to sense and respond to distinct lysosomal stresses

Increased activity of leucine-rich repeat kinase 2 (LRRK2) is an important risk factor for Parkinson’s disease. LRRK2 localizes to lysosomal membranes, and changes in lysosome physiology are emerging ...

doi.org

Bentley-DeSousa, Roczniak-Ferguson and @shawnferguson.bsky.social reveal converging roles of STING and #lysosome damage in activating LRRK2 at #lysosomes via interactions between LRRK2 & GABARAP rupress.org/jcb/article/... 📕 From The Year In Cell Biology: rupress.org/jcb/collecti... #CellBio2025

CRN Team De Camilli reveals a new molecular mechanism that regulates cystine efflux from lysosomes. This work is relevant to #Parkinsons research, as recent studies show JIP4 is downstream of LRRK2. 🔗 Read their #preprint: bit.ly/4l8zCkf ✏️ @shawnferguson.bsky.social @laylanassar.bsky.social

📖Read the latest Advancing Research blog about the impact the @parkinsondotorg.bsky.social 2019 Research Center Award had on PD research at Yale University. @schandralab.bsky.social @shawnferguson.bsky.social @pdc-lab.bsky.social @yaleneuro.bsky.social www.parkinson.org/blog/researc...

From Parkinson’s Foundation Research Center to Powerhouse: How Yale Became a Leader in Parkinson’s Science

parkinson.org

Connecticut cactus flower season 🌵

Carbide Wilson ruins. Gatineau Park, Quebec

Exploring Waterville Valley, NH

I am excited to share our new preprint! Led by @laylanassar.bsky.social , we have found a new JIP4-dependent mechanism that controls the efflux of cystine from lysosomes. Our findings have implications for both lysosome biology and human disease: doi.org/10.1101/2025...

JIP4 deficiency causes a novel lysosome storage disease arising from impaired cystine efflux

Lysosomes break down macromolecules, clear cellular waste and recycle nutrients such as cystine. We describe a novel mechanism whereby JIP4 regulates lysosomal cystine storage by controlling the abundance of cystinosin (CTNS), the transporter responsible for lysosomal cystine efflux. To this end, JIP4, previously characterized as a motor adaptor and kinase signaling scaffold, suppresses TMEM55B-dependent ubiquitylation of CTNS. Loss of JIP4 reduces CTNS protein levels, leading to lysosomal cystine accumulation and lysosomal storage defects that phenocopy loss of CTNS in both human cells and the renal proximal tubules of JIP4 knockout mice. These phenotypes mirror cystinosis, the lysosomal storage disease caused by CTNS loss-of-function. Our findings thus reveal a fundamental process that controls the efflux of lysosomal cystine and has relevance to understanding human disease arising from JIP4 mutations. ### Competing Interest Statement The authors have declared no competing interest. NIH, AG085824, AG062210, R35GM150619 Michael J. Fox Foundation, https://ror.org/03arq3225, ASAP-000580

doi.org

Multiple recent studies, including 3 impressive natural experiments, consistently show a link between Shingles vaccines and reduced dementia. This week a nationwide S Korea study added a reduction of cardiovascular events My summary Table. More here on dementia erictopol.substack.com/p/the-shingl...

Pink lady slipper orchid

Fantastic new study from Raphael Rodriguez' lab shows that induced proximity concepts can be used to induce Ferroptosis! Inducing proximity of lysosomal iron and lipids induces lipid peroxidation! What a cool concept! Have a look at our News/Views with @olzmannlab.bsky.social shorturl.at/cbc8D

Lipid-degrading small molecule kills cancer cells by ferroptosis

A molecule designed to activate iron locked up in organelles called lysosomes and thereby induce cell death might offer a way to tackle treatment-resistant cancer.

shorturl.at

Here’s a new set of discoveries led by Francesca Filippini: doi.org/10.1101/2025... We found that LRP10 promotes the efficient delivery of progranulin to lysosomes and that microglia are particularly sensitive to loss of LRP10.

LRP10 promotes trafficking of progranulin and prosaposin to lysosomes

Mutations in LRP10, a low-density lipoprotein receptor family member, cause familial Parkinson's disease and dementia with Lewy bodies. However, its direct cellular functions remain largely undefined....

doi.org

LRP10 promotes trafficking of progranulin and prosaposin to lysosomes https://www.biorxiv.org/content/10.1101/2025.05.02.651888v1

☕Wang et al. show the recruitment of the #lipid channel protein VPS13C and formation of VPS13C-dependent contacts between endoplasmic reticulum and #lysosomes after lysosomal damage. bit.ly/4jT01lz

The bridge-like lipid transport protein VPS13C/PARK23 mediates ER–lysosome contacts following lysosome damage - Nature Cell Biology

Wang et al. show the recruitment of the lipid channel protein VPS13C and formation of VPS13C-dependent contacts between endoplasmic reticulum and lysosomes after lysosomal damage.

bit.ly