MOLECULAR CHARACTERIZATION OF THE INTRACELLULAR TRAFFIC OF LRP1 AND ALPHA 2-M/LRP1 COMPLEX¡¨

JALDIN FINCATI JR; BARCELONA PF; SANCHEZ MC; CHIABRANDO GA

Congreso; SAIB 2010 (XLVI Reunión Anual de Sociedad Argentina en Bioquímica y Biología Molecular).; 2010

The LDL receptor-related protein 1 (LRP1) is an endocytic receptor

involved in the á2-Macroglubulin (á2M*) internalization.

Previously we demonstrated that LRP1 mediated the á2M*-

induced intracellular signaling activation. However, the molecular

regulation of the LRP1 signaling and endocytosis activity are not

well established. In this work we tried to characterize the LRP1

intracellular traffic with Alexa-Fluor á2M* using pull-chase

experiments at 37 °C (0 to 60 min) with a previous binding step at 4

°C (30 min). The intracellular localization of Alexa-Fluor á2M*

was examined by confocal microscopy using specific fluorescent

antibodies against intracellular vesicles. The clatrin-mediated

endocytosis of LRP1 and á2M*/LRP1 complex was compared with

transferring receptor (TfR), using Alexa-Fluor Tf, and specifically

blocked by a negative Eps15 mutant (EÄ95/295). Our data

demonstrated that á2M* is clatrin-dependent internalized by LRP1,

since it was fully blocked in cells transiently expressing EÄ95/295.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

since it was fully blocked in cells transiently expressing EÄ95/295.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

demonstrated that á2M* is clatrin-dependent internalized by LRP1,

since it was fully blocked in cells transiently expressing EÄ95/295.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

since it was fully blocked in cells transiently expressing EÄ95/295.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

transferring receptor (TfR), using Alexa-Fluor Tf, and specifically

blocked by a negative Eps15 mutant (EÄ95/295). Our data

demonstrated that á2M* is clatrin-dependent internalized by LRP1,

since it was fully blocked in cells transiently expressing EÄ95/295.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

since it was fully blocked in cells transiently expressing EÄ95/295.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

demonstrated that á2M* is clatrin-dependent internalized by LRP1,

since it was fully blocked in cells transiently expressing EÄ95/295.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

since it was fully blocked in cells transiently expressing EÄ95/295.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

was examined by confocal microscopy using specific fluorescent

antibodies against intracellular vesicles. The clatrin-mediated

endocytosis of LRP1 and á2M*/LRP1 complex was compared with

transferring receptor (TfR), using Alexa-Fluor Tf, and specifically

blocked by a negative Eps15 mutant (EÄ95/295). Our data

demonstrated that á2M* is clatrin-dependent internalized by LRP1,

since it was fully blocked in cells transiently expressing EÄ95/295.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

since it was fully blocked in cells transiently expressing EÄ95/295.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

Then, we show that LRP1-á2M complex is localized in early

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

endosomes at 10 min of ligand internalization. After this time,

Alexa-Fluor á2M* is localized in late endosomes and lysosomes,

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

whereas LRP1 is in recycling endosomes. Our data suggest that the

signaling activity of LRP1 induced by á2M* occur in the plasmatic

membrane and/or in early endosomes.

membrane and/or in early endosomes.

demonstrated that á2M* is clatrin-dependent internalized by LRP1,

since it was fully blocked in cells transiently expressing EÄ95/295.