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RhoA-Mediated Uptake

This pathway is regulated by GTPase RhoA. This pathway was initially observed while internalization of b-chain of interleukin-2 receptor (IL-2RP) was being investigated. This pathway is independent of clathrin as supported by the fact that IL-2RP uptake was influenced by Rac1, p21 (RAC1) activated kinase 1 (PAK1), and PAK2 [10]. These factors are not involved in CME.

Clathrin-Independent Carriers/Glycosylphosphotidylinositol- Anchored Protein Enriched Early EndosomalCompartments Pathway

Another clathrin- and caveolae-independent mechanism is the CLIC/GEEC pathway. Structurally CLIC/GEEC pathway consists of a ~ 40-nm-wide tube-shaped protrusion along with GTPase regulator. It is associated with focal adhesion kinase-1 (GRAF1) and phosphatidylinositol-4,5-bisphosphate 3-kinase [11]. These membrane carriers are attenuated by cdc42 and ARF1.

Flotillin-Mediated Endocytosis

Flotillins are proteins similar to caveolin-1 embedded in the PM. These proteins appear as a cluster of organized domains within the PM. It has been observed that domains consisting of flotillin get detached from PM in a clathrin-independent manner. Following entry of the vesicles in the cytoplasmic environment, flotillins are found inside multivesicular structures that exhibit close relationship with endosomal processes [12,13].

It has been suggested that flotillin-mediated endocytosis plays a crucial role in nanoparticle uptake. Several studies have shown that flotillin is involved in the uptake ofpoly- plexes and silica nanoparticles. These studies provide evidence of flotillin in endocytic processes that are responsible for nanoparticle entry and trafficking [14,15].

 
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