Adaptor Protein 2 Regulates Receptor-Mediated Endocytosis and Cyst Formation in Giardia lamblia.

RIVERO MR; VRANYCH CV; BISBAL M; MALETTO B; ROPOLO AS; MARIA C. TOUZ

BIOCHEMICAL JOURNAL

PORTLAND PRESS LTD

Año: 2010 vol. 428 p. 33 - 45

0264-6021

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 lamblia 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 predominantly in the endoplasmic reticulum, lysosomal-like peripheral vacuoles, plasma membrane, and nuclei. 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. GlLRP was found to bind directly to the medium subunit of Giardia adaptor protein 2, indicating that receptor-mediated internalization occurs through an adaptin mechanism. Finally, we showed that the degradation of GlLRP was in part due to the action of a γ-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 adaptor protein 2-dependent pathway and possesses a potential role in the intracellular signalling in Giardia.