title: Postsynaptic SDC2 induces transsynaptic signaling via FGF22 for bidirectional synaptic formation.
abstract: Functional synapse formation requires tight coordination between pre- and post-synaptic termini. Previous studies have shown that postsynaptic expression of heparan sulfate proteoglycan syndecan-2 (SDC2) induces dendritic spinogenesis. Those SDC2-induced dendritic spines are frequently associated with presynaptic termini. However, how postsynaptic SDC2 accelerates maturation of corresponding presynaptic termini is unknown. Because fibroblast growth factor 22 (FGF22), a heparan sulfate binding growth factor, has been shown to act as a presynaptic organizer released from the postsynaptic site, it seems possible that postsynaptic SDC2 presents FGF22 to the presynaptic FGF receptor to promote presynaptic differentiation. Here, we show that postsynaptic SDC2 uses its ectodomain to interact with and facilitate dendritic filopodial targeting of FGF22, triggering presynaptic maturation. Since SDC2 also enhances filopodial targeting of NMDAR via interaction with the CASK-mLIN7-MINT1 adaptor complex, presynaptic maturation promoted by FGF22 further feeds back to activate NMDAR at corresponding postsynaptic sites through increased neurotransmitter release and, consequently, promotes the dendritic filopodia-spines (F-S) transition. Meanwhile, via regulation of the KIF17 motor, CaMKII (activated by the NMDAR pathway) may further facilitate FGF22 targeting to dendritic filopodia that receive presynaptic stimulation. Our study suggests a positive feedback that promotes the coordination of postsynaptic and presynaptic differentiation.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.
authors.forename: Hsiao-Tang
authors.initials: HT
authors.lastname: Hu
authors.affiliation: Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Umemori
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Hsueh
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D045744:Cell Line, Tumor; D049229:Dendritic Spines / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism; D016547:Kinesins; D051379:Mice; D008954:Models, Biological; D017729:Presynaptic Terminals / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D011554:Pseudopodia / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D053669:Syndecan-2 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D005346:Fibroblast Growth Factors; D006497:Heparan Sulfate; D016547:Kinesins; D053669:Syndecan-2; C476387:Fgf22 protein, mouse; C000613396:KIF17 protein, rat