positive regulation of receptor-mediated endocytosis involved in cholesterol transport

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of receptor-mediated endocytosis involved in cholesterol transport. [GO_REF:0000058, GOC:BHF, GOC:nc, GOC:TermGenie, PMID:22848640]

Positive regulation of receptor-mediated endocytosis involved in cholesterol transport is a complex biological process that ensures efficient uptake of cholesterol from the bloodstream into cells. This process is tightly regulated and involves a series of coordinated steps:

1. **Ligand Binding:** The process begins with the binding of cholesterol-carrying lipoproteins, such as low-density lipoprotein (LDL), to specific receptors on the cell surface. These receptors, primarily LDL receptors (LDLR), are transmembrane proteins with extracellular domains that recognize and bind to apolipoprotein B (apoB), a protein component of LDL.

2. **Receptor Clustering and Internalization:** Upon ligand binding, LDLRs cluster together in specialized membrane domains called clathrin-coated pits. Clathrin, a protein that forms a cage-like structure, surrounds the pits and facilitates the invagination of the plasma membrane, forming a vesicle containing the LDLR-LDL complex.

3. **Vesicle Transport and Uncoating:** The clathrin-coated vesicle detaches from the plasma membrane and moves towards the early endosome, a sorting compartment within the cell. Inside the early endosome, the acidic environment triggers the dissociation of LDL from LDLR.

4. **Recycling and Degradation:** After releasing LDL, LDLRs can be recycled back to the plasma membrane, ready to bind more cholesterol. However, some LDLRs are targeted for degradation in lysosomes, ensuring that the number of receptors on the cell surface remains balanced. LDL particles are delivered to lysosomes, where they are broken down into free cholesterol and other components.

5. **Cholesterol Transport:** Free cholesterol released from LDL is then incorporated into cellular membranes or stored in cholesterol esters for later use. Cholesterol homeostasis is tightly controlled, with feedback mechanisms regulating the expression and activity of LDLRs to ensure appropriate cholesterol levels within cells.

Positive regulation of receptor-mediated endocytosis involved in cholesterol transport is essential for maintaining cellular cholesterol homeostasis. Dysregulation of this process can lead to various pathologies, including hypercholesterolemia and atherosclerosis, which increase the risk of cardiovascular diseases.'
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