sciencemag.org SCIENCE
RESEARCH
SIGNAL TRANSDUCTION
Activated by interaction
Cytokines trigger immune
responses when they bind to
their cognate receptors. Class I
cytokine receptors rely on the
associated Janus kinase 2
(JAK2) to initiate signal trans-
duction. There has been debate
over whether activation involves
ligand-induced dimerization
of these receptors or ligand-
induced conformational change
of preformed dimers. Wilmes et
al. imaged cytokine receptors in
the plasma membranes of live
human cells by single-molecule
fluorescence microscopy
and observed ligand-induced
dimerization. They found
that the JAK2 pseudokinase
domains contribute to dimeriza-
tion and that hyperactive JAK2
mutants promote dimerization,
consistent with the model that
dimerization triggers activa-
tion. —VV
Science, this issue p. 643
MEDICINE
Clinical uses of cellular
communication
Exosomes are a type of extra-
cellular vesicle that contain
constituents (protein, DNA, and
RNA) of the cells that secrete
them. They are taken up by
distant cells, where they can
affect cell function and behavior.
Intercellular communication
through exosomes seems to be
involved in the pathogenesis
of various disorders, including
cancer, neurodegeneration,
and inflammatory diseases. In
a Review, Kalluri and LeBleu
discuss the biogenesis and
function of exosomes in disease,
highlighting areas where more
research is needed. They
also discuss the potential
clinical applications of exosome
profiling for diagnostics and
exosome-mediated delivery of
therapeutics to target disease
cells. —GKA
Science, this issue p. 640
INFECTIOUS DISEASE
Concern about swine
fever vaccines
African swine fever (ASF) is a
lethal hemorrhagic disease that
affects swine, including wild boar
and domestic pigs. Beginning in
mid-2018 with the introduction
of the ASF virus to China, an out-
break of ASF has devastated pig
farming in Asia. The disease is
spreading into Europe and may
soon become a global threat to
the pig population. Efforts to
prevent the spread of ASF virus
are challenged by residual infec-
tion in the wild boar population
and difficulties in preventing
the movement of pig products.
In a Perspective, Gavier-Widén
et al. discuss strategies to
develop a vaccine that can be
used in bait for wild boar and be
administered to farmed animals
to effectively overcome ASF.
However, in the rush to generate
a vaccine, there are concerns
that the existing options under
development may make matters
worse. —GKA
Science, this issue p. 622
PLANT SCIENCE
Decoupling tillering and
fertilization
For rice as an agricultural crop,
more tillers, or branches that
carry grains, are desired, as
is less demand for nitrogen
fertilization. Unfortunately, for
many rice varieties, the number
of tillers depends on the amount
of nitrogen fertilization. Wu
et al. now show that nitrogen
status affects chromatin func-
tion through modification of
histones, a process in which
the transcription factor NGR5
recruits polycomb repressive
complex 2 to target genes.
Some of these genes regulate
tillering, such that with more
nitrogen, the plants develop
more tillers. NGR5 is regulated
by proteasomal destruction and
mediates hormone signaling. An
increase in NGR5 levels can drive
increases in rice tillering and
yield without requiring increases
in nitrogen-rich fertilizer. —PJH
Science, this issue p. 641
IMMUNOLOGY
A weird way to recognize
phosphoantigens
In contrast to the well-studied
ab T cells, which recognize
peptide antigens presented
by major histocompatibility
complex (MHC) and MHC-like
molecules, how gd T cells recog-
nize antigens remains largely a
mystery. One major class of gd
T cells, designated Vg9Vd 2 +, is
activated by small, phosphoryl-
ated nonpeptide antigens, or
phosphoantigens, produced
by microbes and cancer cells.
Rigau et al. found that these
cells needed the combination
of two immunoglobulin super-
family members, butyrophilin
2A1 (BTN2A1) and BTN3A1, on
their cell surface to recognize
these phosphoantigens. BTN2A1
directly binds the Vg 9 + domain
of the T cell receptor (TCR),
whereas a second ligand, poten-
tially BTN3A1, binds the Vd2 and
g-chain regions on the opposite
side of the TCR. A better under-
standing of this unexpected
form of T cell antigen recogni-
tion should inform and enhance
future gd T cell–mediated immu-
notherapies. —STS
Science, this issue p. 642
CATA LYS I S
Water-selective zeolite
membranes
The yield of many gas-phase
industrial reactions is limited
by the formation of water as a
by-product. Li et al. harnessed
the water-sieving properties of
NaA zeolite crystals by forming
them into continuous defect-
free membranes within tube
reactors (see the Perspective
by Carreon). These membranes
can let water pass but reject
gases such as hydrogen, carbon
monoxide, and carbon dioxide
(CO 2 ). When these membranes
were used in CO 2 hydrogenation
to form methanol with water
as a by-product, substantial
increases were observed in both
the CO 2 conversion and metha-
nol yield. —PDS
Science, this issue p. 667;
see also p. 624
NEUROSCIENCE
Microglia modulate
memories
Synaptic reorganization and
circuit rewiring leads to loss
or weakening of connections
between neurons and may result
in the erasure of previously
formed memories. Microglia
eliminate excessive synapses in
the developing brain and regu-
late the dynamics of synaptic
connections between neurons
throughout life. However, it is
still unclear whether forgetting is
related to microglia activity and
how microglia regulate memory
erasure in the adult brain. Wang
et al. discovered that microglia
eliminated synaptic compo-
nents in the adult hippocampus
and that depleting microglia
or inhibiting phagocytosis of
microglia prevented forgetting.
Synapse elimination by microglia
may thus lead to degradation of
memory engrams and forgetting
of previously learned contextual
fear memory. —PRS
Science, this issue p. 688
PHASE SEPARATION
Not too sticky
There is increasing evidence for
a role of liquid-liquid phase sepa-
ration (LLPS) in many cellular
processes. Many proteins that
undergo LLPS include prion-
like domains (PLDs), which are
enriched in polar amino acids
and often interspersed with
aromatic residues. Combining
experimental data with simula-
tions, Martin et al. quantified
concentrations of PLDs in coex-
isting dilute and dense phases as
Edited by Michael Funk
ALSO IN SCIENCE JOURNALS
639-B 7 FEBRUARY 2020 • VOL 367 ISSUE 6478
Published by AAAS