Unconventional secretion of annexins and galectins

Abstract

Eukaryotic cells have a highly evolved system of protein secretion, and dysfunction in this pathway is associated with many diseases including cancer, infection, metabolic disease and neurological disorders. Most proteins are secreted using the conventional endoplasmic reticulum (ER)/Golgi network and as such, this pathway is well-characterised. However, several cytosolic proteins have now been documented as secreted by unconventional transport pathways. This review focuses on two of these proteins families: annexins and galectins. The extracellular functions of these proteins are well documented, as are associations of their perturbed secretion with several diseases. However, the mechanisms and regulation of their secretion remain poorly characterised, and are discussed in this review. This review is part of a Special Issues of SCDB on 'unconventional protein secretion' edited by Walter Nickel and Catherine Rabouille.

Keywords: Annexins; Galectins; Transport; Unconventional secretion.

Fig. 1

Pathways for unconventional secretion of galectins and annexins. Direct translocation, which may be facilitated or unfacilitated as part of type I secretion, or facilitated by ABC transporters in type II secretion. Export via lysosomes or endosomes, an example of type III secretion. Export in EVs, either via exosomes or via microvesicles; export via exosomes might be an example of type III secretion. It is unclear where annexin found on the surface of EVs originates from. It could come from crossing a membrane in MVBs, and might be transferred from EVs back to the plasma membrane, as indicated by arrows marked with question marks. Brief summaries of the evidence for each protein family using that pathways is shown for annexin in green and for galectin in blue.