Differential distribution of low-density lipoprotein-receptor-related protein (LRP) and megalin in polarized epithelial cells is determined by their cytoplasmic domains

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dc.contributor.authorMarzolo, MP
dc.contributor.authorYuseff, MI
dc.contributor.authorRetamal, C
dc.contributor.authorDonoso, M
dc.contributor.authorEzquer, F
dc.contributor.authorFarfán, P
dc.contributor.authorLi, YH
dc.contributor.authorBu, GJ
dc.date.accessioned2025-01-21T01:09:36Z
dc.date.available2025-01-21T01:09:36Z
dc.date.issued2003
dc.description.abstractMegalin and the low-density lipoprotein (LDL) receptor-related protein (LRP) are two large members of the LDL receptor family that bind and endocytose multiple ligands. The molecular and cellular determinants that dictate the sorting behavior of these receptors in polarized epithelial cells are largely unknown. Megalin is found apically distributed, whereas the limited information on LRP indicates its polarity. We show here that in Madin-Darby canine kidney cells, both endogenous LRP and a minireceptor containing the fourth ligand-binding, transmembrane and LRP cytosolic domains were basolaterally sorted. In contrast, minireceptors that either lacked the cytoplasmic domain or had the tyrosine in the NPTY motif mutated to alanine showed a preferential apical distribution. In LLC-PK1 cells, endogenous megalin was found exclusively in the apical membrane. Studies were also done using chimeric proteins harboring the cytosolic tail of megalin, one with the fourth ligand-binding domain of LRP and the other two containing the green fluorescent protein as the ectodomain and transmembrane domains of either megalin or LRP. Findings from these experiments showed that the cytosolic domain of megalin is sufficient for apical sorting, and that the megalin transmembrane domain promotes association with lipid rafts. In conclusion, we show that LRP and megalin both contain sorting information in their cytosolic domains that directs opposite polarity, basolateral for LRP and apical for megalin. Additionally, we show that the NPTY motif in LRP is important for basolateral sorting and the megalin transmembrane domain directs association with lipid rafts .
dc.fuente.origenWOS
dc.identifier.eissn1600-0854
dc.identifier.issn1398-9219
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96600
dc.identifier.wosidWOS:000182136200007
dc.issue.numero4
dc.language.isoen
dc.pagina.final288
dc.pagina.inicio273
dc.revistaTraffic
dc.rightsacceso restringido
dc.subjectapical
dc.subjectbasolateral
dc.subjectgreen fluorescent protein
dc.subjectlipid rafts
dc.subjectLRP
dc.subjectmegalin
dc.subjectpolarized sorting
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleDifferential distribution of low-density lipoprotein-receptor-related protein (LRP) and megalin in polarized epithelial cells is determined by their cytoplasmic domains
dc.typeartículo
dc.volumen4
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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