SummaryThe CYFIP1/SRA1 gene is located in a chromosomal region linked to various neurological disorders, including intellectual disability, autism, and schizophrenia. CYFIP1 plays a dual role in two apparently unrelated processes, inhibiting local protein synthesis and favoring actin remodeling. Here, we show that brain-derived neurotrophic factor (BDNF)-driven synaptic signaling releases CYFIP1 from the translational inhibitory complex, triggering translation of target mRNAs and shifting CYFIP1 into the WAVE regulatory complex. Active Rac1 alters the CYFIP1 conformation, as demonstrated by intramolecular FRET, and is key in changing the equilibrium of the two complexes. CYFIP1 thus orchestrates the two molecular cascades, protein translation and actin polymerization, each of which is necessary for correct spine morphology in neurons. The CYFIP1 interactome reveals many interactors associated with brain disorders, opening new perspectives to define regulatory pathways shared by neurological disabilities characterized by spine dysmorphogenesis.
CRA Colorado Research Associates (United States) CSIM Centro Sperimentale per l'ldrologia e la Meteorologia (Italy) CVB Constant volume balloons DIAL Differential absorption lidar DLR Deutsches Zentrum fur Luft und Raumfahrt (Germany) DOW Doppler-on-Wheels Radar (NCAR
After 8 years of decay of its ice shelf, Zachariæ Isstrøm, a major glacier of northeast Greenland that holds a 0.5-meter sea-level rise equivalent, entered a phase of accelerated retreat in fall 2012. The acceleration rate of its ice velocity tripled, melting of its residual ice shelf and thinning of its grounded portion doubled, and calving is now occurring at its grounding line. Warmer air and ocean temperatures have caused the glacier to detach from a stabilizing sill and retreat rapidly along a downward-sloping, marine-based bed. Its equal-ice-volume neighbor, Nioghalvfjerdsfjorden, is also melting rapidly but retreating slowly along an upward-sloping bed. The destabilization of this marine-based sector will increase sea-level rise from the Greenland Ice Sheet for decades to come.
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