Bidirectional traffic between the Golgi and the endosomes – machineries and regulation

Abstract

The bidirectional transport between the Golgi complex and the endocytic pathway has to be finely regulated in order to ensure the proper delivery of newly synthetized lysosomal enzymes and the return of sorting receptors from degradative compartments. The high complexity of these routes has led to experimental difficulties in properly dissecting and separating the different pathways. As a consequence, several models have been proposed during the past decades. However, recent advances in our understanding of endosomal dynamics have helped to unify these different views. We provide here an overview of the current insights into the transport routes between Golgi and endosomes in mammalian cells. The focus of the Commentary is on the key molecules involved in the trafficking pathways between these intracellular compartments, such as Rab proteins and sorting receptors, and their regulation. A proper understanding of the bidirectional traffic between the Golgi complex and the endolysosomal system is of uttermost importance, as several studies have demonstrated that mutations in the factors involved in these transport pathways result in various pathologies, in particular lysosome-associated diseases and diverse neurological disorders, such as Alzheimer's and Parkinson's disease.

Early Endosome Morphology in Health and Disease

“…These late endosomes either mature into lysosomes or fuse with pre-existing lysosomes to degrade the cargo (Carpenter and Cohen 1979, Dunn and Maxfield 1992). During maturation of early endosomes to late, some proteins also get shuttled to the trans-Golgi network via the retromer complex (Progida and Bakke 2016). On the other hand, early endosomes undergoing maturation receive membrane proteins and hydrolytic enzymes by fusion of secretory vesicles from the trans-Golgi network, which is essential for the maturation process.…”

Caspases rule the intracellular trafficking cartel

“…The early endosomal compartment is a key sorting station for incoming cargos from the plasma membrane or the TGN for subsequent delivery to specific locations [85][86][87]. Internalized cargos can be either rapidly recycled back to the cell surface following their entry into early endosomes, transported to recycling endosomes for late recycling, or targeted to lysosomes for degradation.…”

The walkoff effect: cargo distribution implies motor type in bidirectional microtubule bundles

“…For example, late endosomes fuse with lysosomes for protein degradation [82]. Similarly, endosomes fuse with the Golgi apparatus, studied here, for protein recycling [83]. The mixing in the cytoplasm by kinesin, is likely to enable the Golgi to cover larger area and facilitate meeting and thus fusing with other compartments.…”