Membrane Trafficking

Group leader
Aitor Hierro
Address

Biofisika Institute (CSIC-UPV/EHU)
Science Park of the UPV/EHU
Barrio Sarriena s/n. 48940 Leioa, Bizkaia (Spain)

Research goal

Living cells constantly recycle receptors, proteins and lipids with a direct impact on nutrient uptake, re-sensitisation to environmental signals, immune surveillance and waste management. Failure to recycle results in reduced signalling, oxidative stress, protein mislocalisation and aggregation, which are pathological hallmarks of many cardiovascular, cancer, and neurodegenerative diseases. Endosomes are key recycling compartments where the biosynthetic and endocytic pathways intersect. Here, the fate of sorting receptors is directly linked to their selective recruitment into tubulo-vesicular carriers. Our understanding of receptor recycling in a motif-dependent manner, the formation of such tubulo-vesicles and the functional components defining their architecture remains very limited. Retromer is a novel protein coat complex with a central role in multiple receptor-sorting events in the endosomes. Retromer combines receptor recruitment with membrane tubulation properties, but unlike other classical coats, it does so through a single-layer or “cage-free” organization.

This laboratory is interested in understanding how retromer components form a coat around tubulo-vesicles, how transmembrane receptors are selectively recruited to control essential cell processes, and how certain pathogens subvert and co-opt these interactions.

Group members
Research Technician
Ikerbasque Research Professor
Research Technician
Publications

Romano-Moreno M, Astorga-Simón EN, Rojas AL, Hierro A

Retromer-mediated recruitment of the WASH complex involves discrete interactions between VPS35, VPS29, and FAM21
Protein Sci. 2024 May;33(5):e4980
doi: 10.1002/pro.4980
Oh C, Buckley PM, Choi J, Hierro A, DiMaio D
Sequence-independent activity of a predicted long disordered segment of the human papillomavirus type 16 L2 capsid protein during virus entry
Proc Natl Acad Sci U S A. 2023 Oct 17;120(42):e2307721120
doi: 10.1073/pnas.2307721120
Lopez-Robles C, Scaramuzza S, Astorga-Simon EN, Ishida M, Williamson CD, Baños-Mateos S, Gil-Carton D, Romero-Durana M, Vidaurrazaga A, Fernandez-Recio J, Rojas AL, Bonifacino JS, Castaño-Díez D, Hierro A.
Architecture of the ESCPE-1 membrane coat
Nat Struct Mol Biol. 2023 Jul;30(7):958-969
doi: 10.1038/s41594-023-01014-7
Guardia CM, Hierro A, Gershlick DC.
Editorial: Energy Requirements in Membrane Trafficking
Front Cell Dev Biol. 2021 Oct 14;9:750633
doi: 10.3389/fcell.2021.750633
Tascón I, Li X, Lucas M, Nelson D, Vidaurrazaga A, Lin YH, Rojas AL, Hierro A, Machner MP
Structural insight into the membrane targeting domain of the Legionella deAMPylase SidD
PLoS Pathog. 2020 Aug 27;16(8):e1008734
doi: 10.1371/journal.ppat.1008734
Baños-Mateos S, Rojas AL, Hierro A
VPS29, a tweak tool of endosomal recycling
Curr Opin Cell Biol. 2019 Aug;59:81-87
doi: 10.1016/j.ceb.2019.03.010