Regulation of LRP-1 expression: Make the point

Emonard, Hervé; Thérêt, Louis; Bennasroune, Amar; Dedieu, Stéphane

doi:10.1016/j.patbio.2014.02.002

Cited by 46 publications

(43 citation statements)

References 105 publications

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“…BECs control the transport of small molecules, such as glucose and amino acids, by expressing specialised solute carrier transporters on the apical (blood) and basal (brain) membranes that pump molecules across one-by-one [6]. BECs overexpress transferrin [7], insulin receptors [8], and low-density lipoprotein receptorrelated protein 1 (LRP1) [9,10,11] and these receptors are often involved in shuttling their respective ligands into trafficking membrane-enveloped carriers across the cell via a process collectively known as transcytosis [12,6]. LRP1 is a critical motif highly expressed by neurons [13] and astrocytes [14], and it has been reported to bind more than 40 ligands [10] undergoing rapid endocytosis with a half-life of less than 30 seconds [15,10].…”

Section: Introductionmentioning

confidence: 99%

On the shuttling across the blood-brain barrier via tubules formation: mechanism and cargo avidity bias

Tian

Leite

Scarpa

et al. 2020

Preprint

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The blood-brain barrier is made of polarised brain endothelial cells (BECs) phenotypically conditioned by the central nervous system (CNS). Transport across BECs is of paramount importance for nutrient uptake as well as to rid the brain of waste products. Nevertheless,currently we do not understand how large macromolecular cargo shuttles across and how BECs discriminate between the brain-bound and own nutrients. Here, we study the low-density lipoprotein receptor-related protein 1 (LRP1) an essential regulator of BEC transport, and show that it is associated with endocytic effectors, endo-lysosomal compartments as well as syndapin-2, a member of the Bin/Amphiphysin/Rvs (BAR) domain superfamily known to stabilise tubular carriers. We employed synthetic self-assembled vesicles, polymersomes, as a multivalent system with tunable avidity as a tool to investigate the mechanism of transport across BECs. We used a combination of conventional and super-resolution microscopy, both in vivo and in vitro, accompanied with biophysical modelling of transport kinetics and membrane-bound interactions. Our results demonstrate that the avidity of the ligand-receptor interaction (the overall cargo binding energy) determines the mechanism of sorting during the early stages of endocytosis and consequent trafficking. We show that high avidity cargo biases the LRP1 towards internalisation and fast degradation in BECs, while mid avidity augments the formation of syndapin-2 stabilised tubular carriers and promotes fast shuttling across BECs. Thus, we map out a very detailed mechanism where clathrin, actin, syndapin-2, dynamin and SNARE act synergistically to enable fast shuttling across BECs.

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Section: Introductionmentioning

confidence: 99%

On the shuttling across the blood-brain barrier via tubules formation: mechanism and cargo avidity bias

Tian

Leite

Scarpa

et al. 2020

Preprint

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“…The extracellular α chain harbors four LDLR ligand-binding repeats that interact with about 40 ligands, whereas the transmembrane β-chain contains an extracellular portion, a transmembrane domain, and a short cytoplasmic tail that includes two NPxY motifs for triggering endocytosis and recruiting adaptor and signaling proteins. 21 LRP-1 regulates extracellular proteolytic activities by mediating the endocytic clearance of all active proteinases (including metalloproteinases) bound to the pan-proteinase inhibitor α 2 -macroglobulin. 19 More specifically, LRP-1 endocytoses members of the matrix metalloproteinase (MMP) family, MMP-2, MMP-9, and MMP-13, and members of the adamalysin-like metalloproteinase with thrombospondin (TSP) motifs (ADAMTS) family, ADAMTS-4 and ADAMTS-5.…”

Section: Lrp-1mentioning

confidence: 99%

Low-density lipoprotein receptor-related protein in metalloproteinase-mediated pathologies: recent insights

Emonard

Marbaix²

2015

MNM

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Low-density lipoprotein receptor-related protein (LRP)-1, LRP-1b, LRP-2, LRP-5, and LRP-6 mediate the endocytosis of metalloproteinases and inhibitors and/or promote the expression of metalloproteinases. These properties confer important and complex roles in the development of pathologies related to an intense proteolytic degradation of the cellular microenvironment. The cell surface levels of the identified endocytic receptors, LRP-1, LRP-1b, and LRP-2, are themselves regulated by metalloproteinases. The released extra-and intracellular domains may also exert functions in these pathologies.

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“…O LRP-1 é um receptor endocítico pertencente à família do receptor de LDL (Emonard et al, 2014) e é abundantemente expresso em tecidos do fígado, cérebro, placenta (Pires et al, 2012;Emonard et al, 2014) e parede vascular associado principalmente a macrófagos e células de músculo liso (Llorent-Cortés & Badimon, 2005).…”

Section: Discussionunclassified

“…O LRP-1 reconhece a apoproteína E (apoE) e interage com no mínimo 40 diferentes ligantes desde lipoproteínas, glicoproteínas da matriz extracelular, proteases, vírus, citocinas e fatores de crescimento, sendo um receptor importante envolvido em processos fisiológicos e patológicos (Boucher & Herz, 2011;Emonard et al, 2014).…”

Section: Discussionunclassified

Uso de carmustina associada a nanoemulsões ricas em colesterol (LDE) para tratamento da aterosclerose induzida em coelhos

Daminelli¹

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Regulation of LRP-1 expression: Make the point

Cited by 46 publications

References 105 publications

On the shuttling across the blood-brain barrier via tubules formation: mechanism and cargo avidity bias

On the shuttling across the blood-brain barrier via tubules formation: mechanism and cargo avidity bias

Low-density lipoprotein receptor-related protein in metalloproteinase-mediated pathologies: recent insights

Uso de carmustina associada a nanoemulsões ricas em colesterol (LDE) para tratamento da aterosclerose induzida em coelhos

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