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Reposted by Julian Nüchel

Journal of Cell Science @jcellsci.bsky.social · 09/09/2026

Susanne Steigleder, Julian Nüchel @jnuechel.bsky.social, Marius Lemberg @marius-lemberg.bsky.social and colleagues identify a Golgi-bypass secretion mechanism for proTGFα involving TMED9 and GRASP65. journals.biologists.com/jcs/article/...

Proposed mechanism of TMED9- and GRASP65-induced unconventional proTGFα secretion.

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Julian Nüchel @jnuechel.bsky.social · 01/09/2026

Brandnew preprint from @marius-lemberg.bsky.social @bccologne.bsky.social and my lab ! Great to be Part of this collaboration!

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Reposted by Julian Nüchel

Biochemistry Center Cologne @bccologne.bsky.social · 23/07/2026

Congratulations to our junior group leader @bccologne @unicologne Julian Nüchel on this exciting preprint! The study identifies TANGO1 as a selective ECM cargo receptor, revealing new insights into ER export and skeletal dysplasia. A collaborative milestone from FOR2722

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Reposted by Julian Nüchel

medRxivpreprint @medrxivpreprint.bsky.social · 23/07/2026

A conserved cargo recognition mechanism establishes TANGO1 as a selective extracellular matrix cargo receptor www.medrxiv.org/content/10.64898/20…

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Julian Nüchel @jnuechel.bsky.social · 23/07/2026

10/10 Bottom line: TANGO1 isn’t a generic “big cargo” gatekeeper. It’s a bona fide selective ECM cargo receptor, working independently of HSP47.

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Julian Nüchel @jnuechel.bsky.social · 23/07/2026

9/10 This also resolves a puzzle: losing single TANGO1 clients like COL6A3 or COL12A1 alone causes distinct, milder myopathies,not skeletal dysplasia. Losing TANGO1 hits several of them plus collagen-modifying enzymes at once. It’s likely the combination that drives the phenotype

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Julian Nüchel @jnuechel.bsky.social · 23/07/2026

8/10 Why it matters for patients: we found new MIA3 variants (in this same domain) in people with a skeletal dysplasia. Patient fibroblasts show selective ER retention of the same TANGO1-dependent cargo — not a generic secretory traffic jam. 🚗🚙

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Julian Nüchel @jnuechel.bsky.social · 23/07/2026

7/10 One residue does most of the work: a conserved tyrosine (Y75) in the MOTH domain. Upon mutation, cargo binding does not work anymore, and cells phenocopy full TANGO1 knockout for the exact same client set.

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Julian Nüchel @jnuechel.bsky.social · 23/07/2026

6/10 That pattern only makes sense if TANGO1 is reading sequence/structure, not just size. So we mapped the interface: the luminal MOTH domain of TANGO1 directly binds the C3–C4 region of COL6A3 and a specific FBN2 fragment — HSP47-independent

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Julian Nüchel @jnuechel.bsky.social · 23/07/2026

5/10 Even weirder: TANGO1 dependency splits within collagen families. Same size, same family, completely different fate. So the size alone is (again) not the most important feature 😉

static.klipy.com

Luke Skywalker in Book of Boba Fett: Size Matters Not

ALT: Luke Skywalker in Book of Boba Fett: Size Matters Not

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Julian Nüchel @jnuechel.bsky.social · 23/07/2026

4/10 We compared the secretomes of TANGO1-KO and HSP47-KO fibroblasts. If HSP47 were just TANGO1’s adaptor, their cargo lists should overlap a lot. They barely do. TANGO1 loss hits COL6A3, COL1A2, COL12A1, FBN2 and more. HSP47 loss hits a different set (BM Proteins)

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Julian Nüchel @jnuechel.bsky.social · 23/07/2026

3/10 Collagens and fibrillins are often too big for normal ER to Golgi Transport carriers. TANGO1 was known to help export this “bulky cargo” — but the field debated whether it does this directly, or only via the chaperone HSP47.

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Julian Nüchel @jnuechel.bsky.social · 23/07/2026

2/10 we show that TANGO1 (MIA3) doesn’t just help big collagens leave the ER — it directly reads out which collagens and fibrillins to grab. 🧵

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Julian Nüchel @jnuechel.bsky.social · 10/07/2026

First Nüchel Lab Outing - Paintball

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Julian Nüchel @jnuechel.bsky.social · 13/01/2026

New preprint 👇🏻👇🏻👇🏻

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