Dendritic spines are the major locations of excitatory synapses in the mammalian central nervous system. The transformation from dendritic filopodia to dendritic spines has been recognized as one type of spinogenesis. For instance, syndecan-2 (SDC2), a synaptic heparan sulfate proteoglycan, is highly concentrated at dendritic spines and required for spinogenesis. It induces dendritic filopodia formation, followed by spine formation. However, the molecular regulation of the filopodium-spine transition induced by SDC2 is still unclear. In this report, we show that calcium is an important signal downstream of SDC2 in regulation of filopodium-spine transition but not filopodia formation. SDC2 interacted with the postsynaptic proteins calmodulin-dependent serine kinase (CASK) and LIN7 and further recruited NMDAR to the tips of filopodia induced by SDC2. Calcium influx via NMDAR promoted spine maturation because addition of EGTA or AP5 to the culture medium effectively prevented morphological change from dendritic filopodia to dendritic spines. Our data also indicated that F-actin rearrangement regulated by calcium influx is involved in the morphological change, because the knockdown of gelsolin, a calcium-activated F-actin severing molecule, impaired the filopodium-spine transition induced by SDC2. In conclusion, our study demonstrates that postsynaptic proteins coordinate to trigger calcium signalling and cytoskeleton rearrangement and consequently control filopodium-spine transition.
Keywords: CASK; LIN7; NMDAR; Syndecan-2; dendritic spinogenesis.
© 2014 Wiley Periodicals, Inc.