Transporter membrane traffic and function: lessons from a mould.
George DiallinasOlga MartzoukouPublished in: The FEBS journal (2019)
Transporters are essential transmembrane proteins that mediate the selective translocation of solutes, ions or drugs across biological membranes. Their function is related to cell nutrition, communication, stress resistance and homeostasis. Consequently, their malfunction is associated with genetic or metabolic diseases and drug sensitivity or resistance. A distinctive characteristic of transporters is their cotranslational translocation and folding in a membrane bilayer, this being the endoplasmic reticulum (ER) in eukaryotes or the cell membrane in prokaryotes. In the former case, transporters exit the ER packed in secretory vesicles and traffic via seemingly unconventional, rather than Golgi-dependent, sorting routes to their final destination, the plasma membrane (PM). Proper folding is a prerequisite for ER exit and further trafficking. Misfolded transporters, either due to mutations, high temperature of chemical agents (e.g. DMSO, DTT) are blocked in the ER. The accumulation of ER-retained transporters, in most cases, elicits endoplasmic reticulum-associated degradation, but also ubiquitination-dependent, chaperone-mediated, selective autophagy. The function of PM transporters is finely regulated at the cellular level, in response to physiological or stress signals that promote, via α-arrestin-assisted ubiquitination, their endocytosis and vacuolar/lysosomal degradation, and in some cases recycling to the PM. Importantly, transporter oligomerization and specific interactions with membrane lipids are emerging as important players in transporter expression, function and turnover. This review discusses how paradigmatic work on transporters of a model mould, Aspergillus nidulans, has contributed to novel findings related to transporter functioning in eukaryotes.
Keyphrases
- endoplasmic reticulum
- air pollution
- particulate matter
- heavy metals
- high temperature
- poor prognosis
- cell death
- physical activity
- emergency department
- single cell
- polycyclic aromatic hydrocarbons
- endoplasmic reticulum stress
- stem cells
- molecular dynamics simulations
- transcription factor
- water soluble
- quantum dots
- risk assessment
- copy number
- stress induced
- long non coding rna
- binding protein