Science - 31 January 2020

(Marcin) #1
sciencemag.org SCIENCE

RESEARCH | IN OTHER JOURNALS


physiological relevance has not
been explored. Yan et al. studied
two different experimental
mouse tumor models and
found that MAIT cells promoted
lung metastasis by quashing
natural killer cell activity. The
researchers could block this
effect and reduce metastasis
by using inhibitory antibodies
against MR1. Targeting the MAIT
cell–MR1 axis may represent an
emerging strategy for cancer
immunotherapy. —PNK
Cancer Discov. 10 , 124 (2020).


CELL BIOLOGY


The cellular architecture


of ERAD


Endoplasmic reticulum (ER)–
associated degradation (ERAD)
is an evolutionarily conserved
quality control mechanism
whereby misfolded proteins
are removed from the ER and
degraded in the cytosol by the
ubiquitin-proteasome system.
Many ERAD-mediating proteins
have been identified, but their
spatial organization within the
cell is less well established.
Albert et al. used in situ cryo–
electron tomography to image
the native molecular land-
scape within Chlamydomonas
cells. They found that ERAD
proteins concentrated within


~200-nanometer cytosolic foci
that contacted the ER mem-
brane away from the ER-Golgi
interface. The ribosome-exclud-
ing ERAD microcompartments
consisted of a core of clustered
proteasomes surrounded by
Cdc48. Within these clusters,
active proteasomes appeared to
engage directly with substrates
at the ER membrane, a func-
tion thought to be performed
by Cdc48. In live-cell imaging
experiments, the proteasome
clusters were seen to form
dynamically, possibly by liquid-
liquid phase separation. This
dynamic, but well-defined,
architecture of ERAD machinery
likely contributes to efficient
protein quality control. —SMH
Proc. Natl. Acad. Sci. U.S.A. 117 , 1069
(2020).

NEUROSCIENCE
Fast and slow recycling of
synaptic vesicles
The function of microtubules
and filamentous actin in mature
synapses is not fully under-
stood. Using confocal and
stimulated emission depletion
microscopy on a giant audi-
tory synapse of the rat nervous
system, termed the calyx of
Held, Babu et al. found that
microtubules extended into

terminal swellings and were par-
tially colocalized with synaptic
vesicles. Depolymerization of
microtubules in calyceal termi-
nals prolonged the recovery of
excitatory postsynaptic currents
from short-term depression,
whereas fast recovery from
short-term depression was
prolonged by depolymeriza-
tion of filamentous actin. These
results reveal distinct contribu-
tions of filamentous actin and
microtubules to synaptic neuro-
transmission and indicate that
these cytoskeletal elements
independently contribute to dif-
ferent aspects of the recycling
of synaptic vesicles. —PRS
J. Neurosci. 40 , 131 (2020).

QUANTUM GASES
Probing a quantum
emulsion
Ultracold atomic gases with
strongly repulsive interactions
can be a useful model system
for studying the emergence
of itinerant ferromagnetism.
However, the same atoms
that can order magnetically
are also prone to pairing into
loosely bound molecules. If
an atomic system is suddenly
placed in a strongly interact-
ing regime, both processes
occur and an inhomogeneous,

phase-separated state con-
sisting of unpaired and paired
atoms can form. Scazza et al.
studied this state with a variety
of probes. The data were con-
sistent with the formation of a
quantum emulsion consisting
of polarized domains coexisting
with paired atoms. The state
was stabilized by low tempera-
tures and strong interactions.
—JS
Phys. Rev. A 101 , 013603 (2020).

MEMBRANE PROTEINS
Simulating deformation
Biological membranes are
jam-packed with proteins and
enzymes that exert forces, both
static and dynamic, on their
adjacent lipids and can cause
local and global changes in mem-
brane curvature. Zhou et al. used
large-scale molecular dynam-
ics simulations to understand
how the membranes around
a small-molecule transporter
deform as the protein undergoes
motions coupled to transport. By
comparing different states of the
transporter, the authors found
that the lipids move with the
transport domains, causing local
deformations of ~10 angstroms
in an area of ~1000 square
angstroms at a cost of 6 to 7
kilocalories per mole. —MAF
eLife 8 , e50576 (2019).

FAT M E TA B O L I S M

Signals from lipid hydrolysis


A


n exploration of how lipolysis is coupled
to mitochondrial changes that increase
oxidative capacity may reveal how a
Mediterranean diet is beneficial. Najt
et al. found that monounsaturated
fatty acids (MUFAs) released by lipolysis
bound to the protein perilipin 5, which car-
ried them to the nucleus. MUFAs also bound
to the deacetylase sirtuin 1 (SIRT1), which
is implicated in the health span–improving
effects of caloric restriction. MUFA binding
increased SIRT1 activity toward certain sub-
strates. Foods like nuts, avocados, and olive
oil all provide MUFAs in the diet, and these
effects could in part underlie their beneficial
properties. —LBR
Mol. Cell 10.1016/j.molcel.2019.12.003 (2020).

Eating a selection of foods that are high in
monounsaturated fatty acids is beneficial for health.

524 31 JANUARY 2020 • VOL 367 ISSUE 6477


PHOTO: PROSTOCK-STUDIO/ALAMY STOCK PHOTO

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