ASCB Newsletter Nov 2013 - page 9

9
NOVEMBER 2013
ASCB
NEWSLETTER
are connected by protein bridges and kept separate to
prevent mixing of the cisternae.)
From Observations to Models
and Back Again
What are the physical principles behind the formation
of the amazing ER sheet structure? This is where our
theoretician partners Misha Kozlov (Tel Aviv) and
Tom Shemesh (now at Harvard Medical School)
came into play. They
demonstrated that the
structure corresponds
to a minimum of elastic
energy of sheet edges
and surfaces. This is
easiest understood if
one considers a single
helicoid. Each point of
the surface is a saddle
point, such that the mean
membrane curvature is
zero (the curvature in one
direction is compensated
by the curvature in the
perpendicular direction).
The bending energy of
the internal edge of the
helicoid would also be
minimal if the proteins
that stabilize sheet edges preferred a negative curvature
of the edge line. Things get a bit more complicated if
there is more than one helicoid connecting the sheets,
but as long as the helicoids have neighbors of the
opposite handedness, the elastic energy is minimized.
What is so gratifying about the collaboration
is that it went continuously back and forth. The
empirical observations gave rise to theoretical models,
which in turn allowed a targeted search for predicted
morphologies. Neither electron microscopy nor
physics alone would have resulted in significant
progress. We hope this example will encourage others
to combine their expertise and tackle similarly exciting
biological problems. Of course, much is left to be
done on our project. One point is that we need to
localize the curvature-stabilizing proteins, perhaps by
using green fluorescent protein–tagged proteins in
professional secretory cells. But equally challenging
is the development of a theory that would not just
explain individual ER morphologies, but rather
provide some kind of phase diagram in which all
morphologies can be predicted on the basis of the
concentrations of morphogenic proteins.
n
—Tom A. Rapoport, Harvard Medical School, and
Mark Terasaki, University of Connecticut Health Center
Note
In addition to those mentioned
above, we want to acknowledge
Narayanan Kasthuri, Robin W.
Klemm, Richard Schalek, Ken J.
Hayworth, Arthur R. Hand, Maya
Yankova, and Greg Huber for their
essential roles in the work described.
References
1
Terasaki M, Shemesh T, Kasthuri N,
Klemm RW, Schalek R, Hayworth
KJ, Hand AR, Yankova M, Huber G,
Lichtman JW, Rapoport TA, Kozlov
MM (2013). Stacked endoplasmic
reticulum sheets are connected by
helicoidal membrane motifs.
Cell
154, 285–296.
2
Shibata Y, Hu J, Kozlov MM,
Rapoport TA (2009). Mechanisms
shaping the membranes of cellular organelles.
Annu Rev Cell
Dev Biol
25, 329–354.
3
Chen S, Novick P, Ferro-Novick S (2013). ER structure and
function.
Curr Opin Cell Biol
25, 428–433.
4
Voeltz GK, Prinz WA, Shibata Y, Rist JM, Rapoport TA
(2013). A class of membrane proteins shaping the tubular
endoplasmic reticulum.
Cell
124, 573–586.
5
Orso G, Pendin D, Liu S, Tosetto J, Moss TJ, Faust JE,
Micaroni M, Egorova A, Martinuzzi A, McNew JA, Daga
A (2009). Homotypic fusion of ER membranes requires the
dynamin-like GTPase atlastin.
Nature
460, 978–983.
6
Hu J, Shibata Y, Zhu PP, Voss C, Rismanchi N, Prinz WA,
Rapoport TA, Blackstone C (2009). A class of dynamin-
like GTPases involved in the generation of the tubular ER
network.
Cell
138, 549–561.
7
Shibata Y, Shemesh T, Prinz WA, Palazzo AF, Kozlov
MM, Rapoport TA (2010). Mechanisms determining the
morphology of the peripheral ER.
Cell
143, 774-788.
Credit: Sidney Tamm
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