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Publication : Fatty-acid-binding protein 5 controls retrograde endocannabinoid signaling at central glutamate synapses.

First Author  Haj-Dahmane S Year  2018
Journal  Proc Natl Acad Sci U S A Volume  115
Issue  13 Pages  3482-3487
PubMed ID  29531087 Mgi Jnum  J:281264
Mgi Id  MGI:6150699 Doi  10.1073/pnas.1721339115
Citation  Haj-Dahmane S, et al. (2018) Fatty-acid-binding protein 5 controls retrograde endocannabinoid signaling at central glutamate synapses. Proc Natl Acad Sci U S A 115(13):3482-3487
abstractText  Endocannabinoids (eCBs) are lipid-signaling molecules involved in the regulation of numerous behaviors and physiological functions. Released by postsynaptic neurons, eCBs mediate retrograde modulation of synaptic transmission and plasticity by activating presynaptic cannabinoid receptors. While the cellular mechanisms by which eCBs control synaptic function have been well characterized, the mechanisms controlling their retrograde synaptic transport remain unknown. Here, we demonstrate that fatty-acid-binding protein 5 (FABP5), a canonical intracellular carrier of eCBs, is indispensable for retrograde eCB transport in the dorsal raphe nucleus (DRn). Thus, pharmacological inhibition or genetic deletion of FABP5 abolishes both phasic and tonic eCB-mediated control of excitatory synaptic transmission in the DRn. The blockade of retrograde eCB signaling induced by FABP5 inhibition is not mediated by impaired cannabinoid receptor function or reduced eCB synthesis. These findings indicate that FABP5 is essential for retrograde eCB signaling and may serve as a synaptic carrier of eCBs at central synapses.
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