Journal
SCIENCE ADVANCES
Volume 6, Issue 48, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abc4397
Keywords
-
Categories
Funding
- ERC [MEViC 278793, CheSSTaG 769798]
- EPSRC/BTG Healthcare Partnership [EP/I001697/1]
- EPSRC Established Career Fellowship [EP/N026322/1]
- EPSRC/SomaNautix Healthcare Partnership [EP/R024723/1]
- Children with Cancer UK [16-227]
- Royal Society
- Marie Sklodowska-Curie Actions
- EPSRC [EP/N026322/1, EP/I001697/1] Funding Source: UKRI
Ask authors/readers for more resources
The blood-brain barrier is made of polarized brain endothelial cells (BECs) phenotypically conditioned by the central nervous system (CNS). Although transport across BECs is of paramount importance for nutrient uptake as well as ridding the brain of waste products, the intracellular sorting mechanisms that regulate successful receptor-mediated transcytosis in BECs remain to be elucidated. Here, we used a synthetic multivalent system with tunable avidity to the low-density lipoprotein receptor-related protein 1 (LRP1) to investigate the mechanisms of transport across BECs. We used a combination of conventional and super-resolution microscopy, both in vivo and in vitro, accompanied with biophysical modeling of transport kinetics and membrane-bound interactions to elucidate the role of membrane-sculpting protein syndapin-2 on fast transport via tubule formation. We show that high-avidity cargo biases the LRP1 toward internalization associated with fast degradation, while mid-avidity augments the formation of syndapin-2 tubular carriers promoting a fast shuttling across.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available