Unconventional Protein Transport Across the Golgi Ribbon

In addition to the classical secretory pathway, which involves the transport of endoplasmic reticulum (ER)-derived cargo through the cisternal stacks of the Golgi apparatus, several Golgi-independent transport routes contribute to the delivery of membrane-bound and soluble proteins to the plasma membrane (PM) or the extracellular space. Some of these transport events bypassing the Golgi stacks-collectively referred to as unconventional protein secretion (UcPS)-employ vesicular intermediates. However, the nature of these intermediates and the intracellular pathways utilized by various unconventional cargo are only partly understood. Notably, beyond its role in conventional secretory trafficking at the ER-Golgi interface, the intermediate compartment (IC) has been identified at the crossroads of two distinct vesicular UcPS pathways, participating in the sorting and Golgi-independent trafficking of both ER-synthesized (ER translocation signal-containing) and leaderless cytoplasmic cargo. Additionally, findings indicating that the IC directly interacts with the endocytic recycling system may help clarify how various unconventional cargo proteins reach the cell surface. Given that the central IC elements and recycling endosomes (REs)-defined by the GTPases Rab1 and Rab11, respectively-are closely associated with, and may even link the Golgi stacks, this chapter explores the connection between the classical and unconventional secretory routes and their potential divergence at the level of the Golgi ribbon.