Transcytose

Transcytosis is a cellular transport process that moves macromolecules across the interior of a polarized cell, typically from one plasma membrane domain to the opposite domain. It involves uptake at one surface, passage through endocytic compartments, and exocytosis at the other surface. This mechanism is especially important in epithelial and endothelial cells lining mucosal surfaces and blood vessels.

Mechanistically, cargo is internalized by endocytosis, trafficked within vesicular carriers—often along microtubules—through endosomal compartments, and sorted for release on the opposite side. The route may involve clathrin-coated or caveolar vesicles, and sorting receptors help direct specific cargo.

Two major variants are recognized: receptor-mediated transcytosis (RMT) and adsorptive transcytosis. RMT uses specific cell-surface receptors such as the transferrin receptor, Fc receptor for IgG (FcRn), or low-density lipoprotein receptor–related proteins to capture and ferry ligands across the cell. Adsorptive transcytosis depends on electrostatic interactions that promote uptake of positively charged molecules without a dedicated receptor.

Physiological roles include transfer of maternal antibodies to the fetus via FcRn in the placenta, absorption of certain macromolecules across neonatal and intestinal epithelia in some species, and transport across endothelial barriers to distribute proteins such as albumin and transferrin. Transcytosis at the blood–brain barrier also contributes to CNS homeostasis, albeit in a limited and tightly regulated manner.

Pathogens and therapeutics exploit transcytotic pathways: some viruses and bacteria hijack transcytosis to cross mucosal barriers, while researchers seek to design drugs and nanoparticles that leverage transcytosis to reach protected tissues. Understanding transcytosis informs vaccine delivery, antibody therapy, and drug delivery across barriers.