Unconventional Pathways of Protein Secretion: Mammals vs. Plants

Abstract

In eukaryotes, many proteins contain an N-terminal signal peptide that allows their translocation into the endoplasmic reticulum followed by secretion outside the cell according to the classical secretory system. However, an increasing number of secreted proteins lacking the signal peptide sequence are emerging. These proteins, secreted in several alternative ways collectively known as unconventional protein secretion (UPS) pathways, exert extracellular functions including cell signaling, immune modulation, as well as moonlighting activities different from their well-described intracellular functions. Pathways for UPS include direct transfer across the plasma membrane, secretion from endosomal/multivesicular body-related components, release within plasma membrane-derived microvesicles, or use of elements of autophagy. In this review we describe the mammals and plants UPS pathways identified so far highlighting commonalities and differences.

Keywords: cell signaling; extracellular space; extracellular vesicles; unconventional protein secretion; vacuole.

FIGURE 1

Overview of unconventional protein secretion (UPS) pathways in mammals and plants, with a description of proteins following different UPS routes. From left to right: UPS type I, UPS type II, and UPS type III are used by leaderless proteins which employ different methods to go through the plasma membrane (PM). In type III autophagosomes are inserted to represent the crosstalk between UPS and autophagy (see Paragraph 1.1.3). The scheme of UPS type IV represents the destiny of SP/transmembrane domain-containing proteins translocated in the ER, the next journey to the plasma membrane in mammals, and the direct delivery to the vacuole in plants. However, such proteins normally traffic along the conventional secretory pathway and transit through the Golgi apparatus.