Abstract
Looking at the variety of the thousands of different polypeptides that have been focused on in the research on the endoplasmic reticulum from the last five decades taught us one humble lesson: no one size fits all. Cells use an impressive array of components to enable the safe transport of protein cargo from the cytosolic ribosomes to the endoplasmic reticulum. Safety during the transit is warranted by the interplay of cytosolic chaperones, membrane receptors, and protein translocases that together form functional networks and serve as protein targeting and translocation routes. While two targeting routes to the endoplasmic reticulum, SRP (signal recognition particle) and GET (guided entry of tail-anchored proteins), prefer targeting determinants at the N- and C-terminus of the cargo polypeptide, respectively, the recently discovered SND (SRP-independent) route seems to preferentially cater for cargos with non-generic targeting signals that are less hydrophobic or more distant from the termini. With an emphasis on targeting routes and protein translocases, we will discuss those functional networks that drive efficient protein topogenesis and shed light on their redundant and dynamic nature in health and disease.
Highlights
Eucaryotic cells use the principle of compartmentalization to streamline the flow of information within the crowded intracellular environment
The recent observation of a dual recognition of GPI-anchored proteins at both termini may argue for such a scenario [43], where the C-terminus is captured by an SND component and the N-terminus by signal recognition particle (SRP) for subsequent targeting to the Sec61 complex
The original idea of a single targeting factor, a single receptor, and a single protein translocase has been massively expanded during the last years and a variety of targeting routes and translocases dedicated to the transport of different polypeptide precursors has been shown
Summary
Eucaryotic cells use the principle of compartmentalization to streamline the flow of information within the crowded intracellular environment. Precursor proteins relying on the GET1/2 complex or EMC require a differentially shaped opening compared to the membrane-spanning pore that is provided by the Sec complex. This shows that nature has apparently found more than one solution for polypeptides to traverse a membrane. In light of the macromolecular crowding and potential off-target destinations, one underlying theme that unifies those functional targeting and translocation networks is “safety first” During their journey from the inside of the ribosome to the ER membrane, the nascent polypeptides are handed over from one protected compartment and cavity to the next to avoid extensive folding and premature, unproductive interactions. We will summarize some of these protective micro-compartments and discuss key players of the functional targeting and translocation routes that chaperone polypeptides into or across the ER membrane
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
