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Selective synaptic targeting of the excitatory and inhibitory presynaptic organizers FGF22 and FGF7.
- Source :
-
Journal of cell science [J Cell Sci] 2015 Jan 15; Vol. 128 (2), pp. 281-92. Date of Electronic Publication: 2014 Nov 27. - Publication Year :
- 2015
-
Abstract
- Specific formation of excitatory and inhibitory synapses is crucial for proper functioning of the brain. Fibroblast growth factor 22 (FGF22) and FGF7 are postsynaptic-cell-derived presynaptic organizers necessary for excitatory and inhibitory presynaptic differentiation, respectively, in the hippocampus. For the establishment of specific synaptic networks, these FGFs must localize to appropriate synaptic locations - FGF22 to excitatory and FGF7 to inhibitory postsynaptic sites. Here, we show that distinct motor and adaptor proteins contribute to intracellular microtubule transport of FGF22 and FGF7. Excitatory synaptic targeting of FGF22 requires the motor proteins KIF3A and KIF17 and the adaptor protein SAP102 (also known as DLG3). By contrast, inhibitory synaptic targeting of FGF7 requires the motor KIF5 and the adaptor gephyrin. Time-lapse imaging shows that FGF22 moves with SAP102, whereas FGF7 moves with gephyrin. These results reveal the basis of selective targeting of the excitatory and inhibitory presynaptic organizers that supports their different synaptogenic functions. Finally, we found that knockdown of SAP102 or PSD95 (also known as DLG4), which impairs the differentiation of excitatory synapses, alters FGF7 localization, suggesting that signals from excitatory synapses might regulate inhibitory synapse formation by controlling the distribution of the inhibitory presynaptic organizer.<br /> (© 2015. Published by The Company of Biologists Ltd.)
- Subjects :
- Animals
Carrier Proteins metabolism
Excitatory Postsynaptic Potentials genetics
Fibroblast Growth Factor 7 genetics
Fibroblast Growth Factors genetics
Hippocampus growth & development
Humans
Kinesins metabolism
Membrane Proteins metabolism
Mice
Microtubules metabolism
Synapses physiology
Fibroblast Growth Factor 7 metabolism
Fibroblast Growth Factors metabolism
Hippocampus metabolism
Synapses metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9137
- Volume :
- 128
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of cell science
- Publication Type :
- Academic Journal
- Accession number :
- 25431136
- Full Text :
- https://doi.org/10.1242/jcs.158337