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1.N.7.  The Endomembrane Fusion/Scission/Trafficking (EMFST) Family

Endomembrane trafficking, which allows proteins and lipids to flow between the different endomembrane compartments, largely occurs by vesicle-mediated transport. Transmembrane proteins intended for transport are concentrated into a vesicle or carrier by undulation of a donor membrane. This is followed by vesicle scission, uncoating and, finally, fusion at the target membrane. Three major trafficking pathways operate inside eukaryotic cells: anterograde, retrograde and endocytic (Arora and Van Damme 2021). Each pathway involves a unique set of machinery and coat proteins that pack the transmembrane proteins, along with their associated lipids, into specific carriers. Adaptor and coatomer complexes are major facilitators that function in anterograde transport and in endocytosis. These complexes recognize the transmembrane cargoes destined for transport and recruit the coat proteins that help form the carriers. These complexes use either linear motifs or posttranslational modifications to recognize the cargoes, which are then packaged and delivered along the trafficking pathways. Arora and Van Damme 2021 focus on the different trafficking complexes that share a common evolutionary branch in Arabidopsis thaliana, and they discuss knowledge about the cargo recognition motifs they use. The mechanisms of protein translocation and transmembrane domain insertion into the ER have been summarized, revealing aspects of selective cargo packaging (Sun et al. 2021).

Cells in multicellular organisms are often asymmetric and polarized, maintaining separate membrane domains. Typical examples are the epithelial cells (apical-basal polarization), neurons (dendritic-axonal domains), and migratory cells (with a leading and a trailing edge). Zeke et al. 2021 designed a comprehensive database containing experimentally verified mammalian proteins that display polarized sorting or secretion, focusing on epithelial polarity. Homology-based inferences and transmembrane topology (if applicable) are all provided. The database, PolarProtDb ( offers a detailed interface displaying all information that may be relevant to trafficking, including post-translational modifications (glycosylations and phosphorylations), known or predicted short linear motifs conserved across orthologs, and potential interaction partners (Zeke et al. 2021).

References associated with 1.N.7 family:

Arora, D. and D. Van Damme. (2021). Motif-based endomembrane trafficking. Plant Physiol. [Epub: Ahead of Print] 33605419
Legendre-Guillemin, V., M. Metzler, M. Charbonneau, L. Gan, V. Chopra, J. Philie, M.R. Hayden, and P.S. McPherson. (2002). HIP1 and HIP12 display differential binding to F-actin, AP2, and clathrin. Identification of a novel interaction with clathrin light chain. J. Biol. Chem. 277: 19897-19904. 11889126
Mishra, S.K., N.R. Agostinelli, T.J. Brett, I. Mizukami, T.S. Ross, and L.M. Traub. (2001). Clathrin- and AP-2-binding sites in HIP1 uncover a general assembly role for endocytic accessory proteins. J. Biol. Chem. 276: 46230-46236. 11577110
Sun, S., X. Tang, Y. Guo, and J. Hu. (2021). Endoplasmic reticulum composition and form: Proteins in and out. Curr. Opin. Cell Biol. 71: 1-6. [Epub: Ahead of Print] 33611096
Waelter, S., E. Scherzinger, R. Hasenbank, E. Nordhoff, R. Lurz, H. Goehler, C. Gauss, K. Sathasivam, G.P. Bates, H. Lehrach, and E.E. Wanker. (2001). The huntingtin interacting protein HIP1 is a clathrin and α-adaptin-binding protein involved in receptor-mediated endocytosis. Hum Mol Genet 10: 1807-1817. 11532990
Zeke, A., L. Dobson, L.I. Szekeres, T. Langó, and G.E. Tusnády. (2021). PolarProtDb: A Database of Transmembrane and Secreted Proteins showing Apical-Basal Polarity. J. Mol. Biol. 433: 166705. 33186585