Zellulärer Lipidimport durch Klasse B Scavenger Rezeptoren und die Biogenese von Membrandomänen

Zellulärer Lipidimport durch Klasse B Scavenger Rezeptoren und die Biogenese von Membrandomänen

Beschreibung

vor 17 Jahren
Phospholipids form the matrix of plasmamebranes (PM) consisting of
an asymmetric lipid bilayer. The high amounts of sphingolipids and
cholesterol in the PM are furthermore the basis to form
liquid-ordered domains / rafts by saturated long chain fatty acid
interactions. Hence, the lipid trafficking pathways enabling the
membrane biogenesis and lateral segregation into membrane compounds
remain largely undefined. Here we could demonstrate that the
scavenger receptor CD36 selectively mediates the lipid uptake of
sphingomyelin (SM) and phosphatidylcholine (PC) into PM in an
endocytosis independent way. In human monocytes we could further
show that the selective phospholipid uptake for SM, PC and
phosphatidylethanolamine was almost exclusively promoted by CD36
and SR-BI. Whereas CD36 was mainly localized in rafts, we found
about 2/3rds of SR-BI located in non-rafts. Thereby, the main cell
entrance for phospholipids and cholesterol was mediated by SR-BI
into non-raft compartments. SR-BI was then internalized by
clathrin-coated pits and promoted the formation of intracellular
microdomains in early endosomes by recruitment of the newly
acquired raft lipids. Thus, we propose a leading role for SR-BI in
generating new rafts by the incorporation of the raft building
lipids SM and cholesterol. These may provide a pool for the
regeneration of raft domains within the PM.

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