398 28 JANUARY 2022 • VOL 375 ISSUE 6579 science.org SCIENCEin sciatic nerve tissue was
increased in mice in which
cytohesin-2 phosphorylation
was maintained and decreased
in mice in which phosphorylation
was suppressed. —LKF
Sci. Signal. 15 , eabi5276 (2022).PROTEOMICS
Getting to know our
proteoform
Over the past few years, large-
scale proteomics efforts have
allowed us to begin to under-
stand phenotype at a protein
level. These research efforts
have included studies that map
tissue- and cell-specific protein
compositions. However, proteins
function in the context of modi-
fications that include alternative
splicing and posttranscriptionalSTRUCTURAL BIOLOGY
Nonhallucinogenic
psychedelic analogs
Psychedelic drugs such as
lysergic acid diethylamide
(LSD) and mushroom-derived
psilocybin exert their effects
by binding the serotonin 2A
receptor (5-HT2AR). These
drugs also have antidepressant
effects, but the hallucinations
they cause complicate their
use as therapeutics. Cao et al.
present structures of 5-HT2AR
bound to psychedelic drugs, the
endogenous ligand serotonin,
and the nonhallucinogenic drug
lisuride. The structures reveal
ligand-receptor interactions that
cause a bias toward arrestin
recruitment. Based on these
insights, the authors designed
arrestin-biased ligands thatdisplayed antidepressant-like
activity in mice without hal-
lucination effects. Arrestin
recruitment alone is insufficient
for antidepressant effects, but
the low G-protein signaling of the
arrestin-biased ligands appears
to allow antidepressant effects
without causing hallucination.
—V V
Science, abl8615, this issue p. 403NEUROSCIENCE
Phosphorylation
dynamics for myelination
Myelin sheaths produced by
Schwann cells protect and
insulate the axons of peripheral
neurons, enabling more rapid
neurotransmission. Miyamoto
et al. found that the production
of Schwann cell myelin in miceis regulated by phosphorylation
dynamics at a tyrosine residue
in cytohesin-2. In cultured cells,
the adaptor protein SH2B1
maintained and the phosphatase
PTP4A1 reversed the phosphory-
lation of this residue. MyelinationFalse-color electron microscopy image
of a Schwann cell (center) within a
nerve fi berEurasian reed warblers perceive Earth’s magnetic
field to know where to stop in their migrations.Edited byMichael FunkIN SCIENCE JOURNALS
RESEARCH
ANIMAL MIGRATIONWhere to stop
M
any migratory species undertake
incredibly long migrations through-
out a year. Much research has
focused on understanding how
these animals know where to go and
how to return, and most work has focused
on understanding how animals know—or
learn—routes and directions. Equally impor-
tant, however, is how they know when and
where to stop migrating. Wynn et al. looked
at a century of leg ringing and banding data
in Eurasian reed warblers and found that
the birds rely on the magnetic inclination as
a “stop sign” to return to within meters of
their breeding site. —SNV
Science, abj4210, this issue p. 446PHOTOS: (TOP TO BOTTOM ALAN WILLIAMS; ISTOCK.COM/JOSE LUIS CALVO MARTIN & JOSE ENRIQUE GARCIA MAURIÑO MUZQUIZEurasian reed warblers perceive Earth’s magnetic
field to know where to stop in their migrations.Edited byMichaelFunkIN SCIENCE JOURNALS
ANIMALMIGRATIONWhere to stop
any migratory species undertake
incredibly long migrations through-
out a year. Much research has
focused on understanding how
these animals know where to go and
how to return, and most work has focused
on understanding how animals know—or
learn—routes and directions. Equally impor-
tant, however, is how they know when and
where to stop migrating. Wynn et al. looked
at a century of leg ringing and banding data
in Eurasian reed warblers and found that
the birds rely on the magnetic inclination as
a “stop sign” to return to within meters of
their breeding site. —SNV
Science, abj4210, this issue p. 446