Artificial or synthetic
organelles are a key challenge for bottom-up
synthetic biology. So far, synthetic organelles have typically been
based on spherical membrane compartments, used to spatially confine
selected chemical reactions. In vivo, these compartments are often
far from being spherical and can exhibit rather complex architectures.
A particularly fascinating example is provided by the endoplasmic
reticulum (ER), which extends throughout the whole cell by forming
a continuous network of membrane nanotubes connected by three-way
junctions. The nanotubes have a typical diameter of between 50 and
100 nm. In spite of much experimental progress, several fundamental
aspects of the ER morphology remain elusive. A long-standing puzzle
is the straight appearance of the tubules in the light microscope,
which form irregular polygons with contact angles close to 120°.
Another puzzling aspect is the nanoscopic shapes of the tubules and
junctions, for which very different images have been obtained by electron
microcopy and structured illumination microscopy. Furthermore, both
the formation and maintenance of the reticular networks require GTP
and GTP-hydrolyzing membrane proteins. In fact, the networks are destroyed
by the fragmentation of nanotubes when the supply of GTP is interrupted.
Here, it is argued that all of these puzzling observations are intimately
related to each other and to the dimerization of two membrane proteins
anchored to the same membrane. So far, the functional significance
of this dimerization process remained elusive and, thus, seemed to
waste a lot of GTP. However, this process can generate an effective
membrane tension that stabilizes the irregular polygonal geometry
of the reticular networks and prevents the fragmentation of their
tubules, thereby maintaining the integrity of the ER. By incorporating
the GTP-hydrolyzing membrane proteins into giant unilamellar vesicles,
the effective membrane tension will become accessible to systematic
experimental studies.