Membrane Dynamics

What is clathrin-mediated endocytosis?

Clathrin-mediated endocytosis (CME) is a vesicular transport event that facilitates the internalization and recycling of receptors engaged in a variety of processes, including signal transduction (G-protein and tyrosine kinase receptors), nutrient uptake and synaptic vesicle reformation [1]. Two classical examples of CME are iron-bound transferrin recycling and the uptake of low-density lipoprotein (LDL).

A. Clathrin is a triskelion shaped scaffold protein. B. Clathrin assembles to form a coat around a mature vesicle. C. Formation of the clathrin coated vesicle requires changes in membrane curvature, which is driven by PIP2 levels and BAR protein binding.

CME is characterized by the involvement of clathrin, which is a triskelion-shaped scaffold protein composed of three heavy and three light chains [2][3][4]. Clathrins polymerize around the cytoplasmic face of the invaginated membrane and act as a reinforced mould in which the membrane vesicle may form without direct association with the membrane [5]. Dissociation of the coat occurs rapidly following scission of the vesicle from the membrane.

Initiation of the clathrin complex formation requires the accumulation of phosphatidylinositol‑4,5‑bisphosphate (PIP2) and adaptor proteins, such as AP-2, at the pinching site [6][7][8]. In the case of clathrin-coated vesicles (CCV) formed at the trans-Golgi apparatus (TGA), AP-1 is essential [9][10].

Growth of the clathrin coated pit requires BAR (Bin/Amphiphysin/Rvs) domain proteins [11][12][13] and reorganization of the actin network [14]. The final scission step involves BAR domain proteins, dynamin and the dephosphorylation of PIP2. The latter step is suggested to function within a positive feedback loop, with regards to phosphatase activity [15][16][17]. The vesicles are then transported and sorted, based on receptor type or membrane composition [18], to the various destinations including the trans-Golgi network, endosomes and vacuoles.

References

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