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Apical protein transport

Membranes of epithelial cells are separated by tight junctions into an apical domain facing the organ lumen and a basolateral domain adjacent to neighboring cells or the basal membrane. Both membrane domains differ substantially in their protein and lipid composition. Proteins associated with sphingolipid- and cholesterol-enriched membrane microdomains, the so-called lipid rafts, are predominantly transported to the apical membrane by using rafts as transport platform (sucrase-associated vesicle, SAV). On the other hand, alternative pathways exist for the delivery of non-raft associated cargo molecules to the apical membrane (lactase-associated vesicle, LAV). Raft- and non-raft apical pathways are separated after exit of newly synthesized cargo from the Golgi apparatus. In contrast to the classical view of a direct passage from the Golgi to the apical membrane, our data suggest that endosomes are traversed following Golgi-release and serve as additional sorting organelle for polarized trafficking. Transport machinery of this pathway was analyzed on immunoisolated post-Golgi carriers and comprises specific Rab-GTPases, kinesin motor proteins and adapter molecules for transport like Mx1 or annexins.

Current projects in the group deal with further illumination distinct compartments traversed after Golgi-exit and the cellular machinery involved.

Foto: R.Jacob
Alternative models for apical protein transport. Three scenarios for apical protein sorting are represented in this figure. This may involve transcytosis across the basolateral membrane (scenario I) or direct trafficking routes (scenarios II and III). A classical view of direct transport to the apical membrane describes the sorting of raft-associated (red membrane) and non-associated material in the TGN into apical vesicle populations (II). In the new alternative (III) raft-associated and non-associated cargo is transported jointly to a post Golgi compartment. This compartment segregates apical material into distinct vesicle populations (LAVs and SAVs). ARE, apical recycling endosome; BRE, basolateral recycling endosome; CAV; caveolae; CCP, clathrin coated pits; PGC, post Golgi compartment; TJ, tight junctions.