Unconventional Mechanisms of Protein Transport to the Cell Surface of Eukaryotic Cells

Abstract

The classical secretion of soluble proteins and transport of integral membrane proteins to the cell surface require transit into and through the endoplasmic reticulum and the Golgi apparatus. Signal peptides or transmembrane domains target proteins for translocation into the lumen or insertion into the membrane of the endoplasmic reticulum, respectively. Here we discuss two mechanisms of unconventional protein targeting to plasma membranes, i.e., transport processes that are active in the absence of a functional Golgi system. We first focus on integral membrane proteins that are inserted into the endoplasmic reticulum but that, however, are transported to plasma membranes in a Golgi-independent manner. We then discuss soluble secretory proteins that are secreted from cells without any involvement of the endoplasmic reticulum and the Golgi apparatus.

Role of the Transient Receptor Potential Vanilloid 5 (TRPV5) Protein N Terminus in Channel Activity, Tetramerization, and Trafficking

“…These channels did not display any complex glycosylation, indicating that this small subset of channels reached the plasma membrane without being processed by the Golgi apparatus. Protein targeting to the plasma membrane independent from the Golgi apparatus has been observed by others (40). Finally, we observed that the plasma membrane retrieval of TRPV5-⌬1-38 mutant was delayed.…”

“…Alanine substitution of Gln 31 and Asp 34 rendered a nonfunctional TRPV5 mutant, lacking complex glycosylation. Mutation of three similar residues, Gln 40 , Gln 41 , and Glu 42 , just outside the putative helix did not affect channel function. This indicates that the region around residues 31-34 might be essential for correct folding of the channel or binding of other factors.…”

“…5D). Alanine substitution of three similar residues outside the helix (Gln 40 , Gln 41 , and Glu 42 ), rendering a triple point mutant (QA/QA/EA), did not affect TRPV5 function (Fig. 5C).…”

Straying off the Highway: Trafficking of Secreted Plant Proteins and Complexity in the Plant Cell Wall Proteome

“…Nonclassical or leaderless secretion was first described 20 years ago for two mammalian proteins (Cooper and Barondes, 1990;Rubartelli et al, 1990) and since then considerable progress has been made in characterizing a number of different pathways (Fig. 2) in mammalian and yeast cells, which will not be described in detail here (for review, see Nombela et al, 2006;Nickel and Seedorf, 2008;Prudovsky et al, 2008;Nickel and Rabouille, 2009). It therefore seems likely that nonclassical secretion is common to all eukaryotes, including plants, although this field is essentially unexplored.…”

“…Some hints may come from studies of mammalian proteins, which have been classified into two classes: those that are mostly secreted and those that usually have an intracellular function but that are secreted following specific signals and in specific tissues (Nickel and Seedorf, 2008). It has also been suggested that such secretion can be rapid and activated by external stresses (Keller et al, 2008).…”