Giardia lamblia low‐density lipoprotein receptor‐related protein is involved in selective lipoprotein endocytosis and parasite replication

MR Rivero, SL Miras, R Quiroga… - Molecular …, 2011 - Wiley Online Library
MR Rivero, SL Miras, R Quiroga, AS Rópolo, MC Touz
Molecular microbiology, 2011Wiley Online Library
As Giardia lamblia is unable to synthesize cholesterol de novo, this steroid might be
obtained from the host's intestinal milieu by endocytosis of lipoproteins. In this work, we
identified a putative Giardia lamblia low‐density lipoprotein receptor‐related proteins
(GlLRP), a type I membrane protein, which shares the substrate N‐terminal binding domain
and a FXNPXY‐type endocytic motif with human LRPs. Expression of tagged GlLRP showed
that it was localized predominantly in the endoplasmic reticulum, lysosomal‐like peripheral …
Summary
As Giardia lamblia is unable to synthesize cholesterol de novo, this steroid might be obtained from the host's intestinal milieu by endocytosis of lipoproteins. In this work, we identified a putative Giardia lamblia low‐density lipoprotein receptor‐related proteins (GlLRP), a type I membrane protein, which shares the substrate N‐terminal binding domain and a FXNPXY‐type endocytic motif with human LRPs. Expression of tagged GlLRP showed that it was localized predominantly in the endoplasmic reticulum, lysosomal‐like peripheral vacuoles and plasma membrane. However, the FXNPXY‐deleted GlLRP was retained at the plasma membrane suggesting that it is abnormally transported and processed. The low‐density lipoprotein and chylomicrons interacted with GlLRP, with this interaction being necessary for lipoprotein internalization and cell proliferation. Finally, we show that GlLRP binds directly to the medium subunit of Giardia adaptor protein 2, indicating that receptor‐mediated internalization occurs through an adaptin mechanism.
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