As Giardia lamblia is unable to synthesize cholesterol de novo, this
compound might be obtained from the intestinal milieu by
endocytosis of lipoproteins. Here, we identified a putative Giardia
LRP (GlLRP), a type-I membrane protein, which shares the
substrate-N-terminal binding domain and a FXNPXY-type
endocytic motif with the human Low-density lipoprotein Receptor
related Proteins (LRPs). Expression of tagged-GlLRP showed that
it was localized in the ER, lysosomal-like peripheral vacuoles, PM
and nuclei. However, the FXNPXY-deleted GlLRP was retained at
the PM suggesting that it is abnormally transported and processed.
LDL and chylomicrons interacted with GlLRP, with this interaction
being necessary for lipoprotein internalization. GlLRP was found to
bind directly to the medium subunit of Giardia adaptor protein 2
(AP2), indicating that receptor mediated internalization occurs
through an adaptin mechanism. Beside, by an antisense strategy we
showed that GlLRP plays a pivotal role in parasite replication.
Finally, we showed that the degradation of GlLRP was in part due to
the action of a ã-secretase-like complex, which had a significant
effect in its nuclear localization. We postulate that GlLRP is
involved in the internalization of cholesterol from lipoproteins via a
regulated AP2-dependent pathway and possesses a potential role in
the intracellular signalling.