Rotin_lecture 1_BCH444

found in many other cells they demarcate cholesterol

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: n many other cells. They demarcate cholesterol and sphingolipid-rich microdomains in membranes, where many signaling receptors and transporters are concentrated. -Major protein in caveoli: caveolin (dimer). Inserted into the inner leaflet of the plasma membrane. -Caveolin-1 knockout mice: lack caveoli, but are viable (some problems in lung endothelia) -Tyr phosphorylation (by Src family kinases) can stimulate internalization. -Caveoli internalization is slow (t0.5>20 min) and they include small volumes (50-60 nm diameter), so they do not contribute to majority of fluid-phase endocytosis, except in endothelial cells, where they are very abundant. Actin Fluid-phase endocytosis Also involves Rho family GTPases Stimulated by growth factors Important for dendritic cell function/acquisition of antigens Clathrin mediated endocytosis Principles of directed membrane trafficking: Cargo selection Physical separation donor membrane and transport vesicle Targeting and fusion with target membrane Regulation of cholesterol homeostasis and familial hypercholesterolemia: The case of J.D. Joseph L. Goldstein and Michael S. Brown Normal cell Ferritinlabelled LDL J.D. s cell Ferritinlabelled LDL J.D. s LDL receptor carried a single mutation (Tyrosine to Cystein) in the cytosolic domain (in a NPxY sequence) resulting in hypercholesterolemia due to impaired LDL uptake. WT Receptors are greatly enriched in areas of coated pits and efficiently endocytosed, whereas mutant receptors show even distribution and fail to endocytose Coated pits are site of cargo concentration and endocytosis. Receptor is targeted to coated pits by cytosolic motif. Clathrin mediated endocytosis: A paradigm for coat assisted sorting. Restricted coat assembly at membrane. Cargo concentrat...
View Full Document

This note was uploaded on 03/27/2014 for the course BCH 444 taught by Professor Mccallan during the Spring '14 term at University of Toronto.

Ask a homework question - tutors are online