Critical Determinants in ER-Golgi Trafficking of Enzymes Involved in Glycosylation

Abstract

All living cells generate structurally complex and compositionally diverse spectra of glycans and glycoconjugates, critical for organismal evolution, development, functioning, defense, and survival. Glycosyltransferases (GTs) catalyze the glycosylation reaction between activated sugar and acceptor substrate to synthesize a wide variety of glycans. GTs are distributed among more than 130 gene families and are involved in metabolic processes, signal pathways, cell wall polysaccharide biosynthesis, cell development, and growth. Glycosylation mainly takes place in the endoplasmic reticulum (ER) and Golgi, where GTs and glycosidases involved in this process are distributed to different locations of these compartments and sequentially add or cleave various sugars to synthesize the final products of glycosylation. Therefore, delivery of these enzymes to the proper locations, the glycosylation sites, in the cell is essential and involves numerous secretory pathway components. This review presents the current state of knowledge about the mechanisms of protein trafficking between ER and Golgi. It describes what is known about the primary components of protein sorting machinery and trafficking, which are recognition sites on the proteins that are important for their interaction with the critical components of this machinery.

Keywords: COPI and COPII complexes; ER-Golgi trafficking; glycosyltransferases; mechanism of protein sorting; sequences and motifs involved in trafficking.

Figure 1

The cargo transportation between ER and Golgi via COP-coated cargo carriers. ER: endoplasmic reticulum; COPI: coat protein complex I; COPII: coat protein complex II; ERGIC: ER-Golgi intermediate compartment. Note that the ERGIC compartment has not been demonstrated in plant and yeast cells.

Figure 2

The protein–protein interaction between cargo sorting signal motifs in the GTs and COPI coatomers or cargo receptors. (A): The cargo sorting signal motifs in the cytosolic tail of GTs interact with cargo receptors (e.g., Vps74p and GOLPH3). (B): The GTs interact with putative cargo receptors or directly interact with the COPI complex via cargo sorting signal motifs in the cytosolic tail and/or TMDs. (C): The cargo sorting signal motifs in the cytosolic tail of GTs interact with the MHD domain of δ-COP and β-COP. (D): The cargo sorting signal motifs in the cytosolic tail of GTs interact with the MHD domain of δ-COP, ζ-COP, and β-COP. The figures are created in BioRender.com.

Figure 3

The protein–protein interaction between cargo sorting signal motifs in GTs and COPII coatomers.