Caveolae-Mediated Transcytosis and Its Role in Neurological Disorders

Figures

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  Figure 1. Mechanisms of the endocytosis process. (1) In a static state, caveolin-1 integrates into the plasma membrane (PM) in a COPII-independent manner, leading to lipid sorting, cavin recruitment, and a specific curvature formation of the membrane. (2) Due to mechanical tension from the extracellular matrix (ECM), integral membrane proteins, or ligands released into the circulation, the plasma membrane invaginates and forms caveolae. This process is regulated by kinases (Src, PKC, and Abl) and the depolymerization of the cytoskeleton (Abl/mDia1 and FLNa). Pacsin2, EDH2, and EHBP1 stabilize the neck of the caveolae, preventing their invagination. (3) Endocytic vesicles are transported by microtubules and dynein/kinesin (e.g., KIF13 motor protein). (4) These vesicles are then sorted into either the recycling pathway (e.g., caveolins and receptors) or the secretory pathway (e.g., cargo of transcytosis). The figure was created with BioRender (https://biorender.com/).

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  Figure 2. A summary of the mechanisms of endosome sorting and exocytosis. After endocytosis, (1) Rab5 endocytic vesicles are transported to EEs for sorting. (2) The fusion process of vesicle trafficking is implemented in a SNARE-mediated manner. (3) For nutrient degradation and membrane protein recycling, Rab7 directs the vesicles into LEs, which then fuse with lysosomes. Meanwhile, the vesicles of transcytosis that transport highly lipid-modified ligands are sorted into MVBs and then directed to the plasma membrane for secretion through the ER and GA. Other ligands, such as soluble ones, may be directly sorted into the secretory pathway from EEs. However, the sorting signals for this process are not clear. (4) Eventually, exocytosis is initiated by Munc18 in a SNARE-dependent manner, transporting cargo across the endothelial cells. The figure was created with BioRender.