Regulation of dendritic spine morphology by SPIN90, a novel Shank binding partner.
Dendritic spines are highly specialized actin-rich structures on which the majority of excitatory synapses are formed in the mammalian CNS. SPIN90 is an actin-binding protein known to be highly enriched in postsynaptic densities (PSDs), though little is known about its function there. Here, we show that SPIN90 is a novel binding partner for Shank proteins in the PSD. SPIN90 and Shank co-immunoprecipitate from brain lysates and co-localize in postsynaptic dendrites and act synergistically to mediate spine maturation and spine head enlargement. At the same time, SPIN90 causes accumulation of Shank and PSD-95 within dendritic spines. In addition, we found that the protein composition of PSDs in SPIN90 knockout mice is altered as is the actin cytoskeleton of cultured hippocampal SPIN90 knockout neurons. Taken together, these findings demonstrate that SPIN90 is a Shank1b binding partner and a key contributor to the regulation of dendritic spine morphogenesis and brain function.
Kim
Seon-Myung
SM
Cell Dynamics Research Center and Bioimaging Center, Gwangju Institute of Science and Technology, Gwangju, Korea.
Choi
Kyu Yeong
KY
Cho
In Ha
IH
Rhy
Jin Hee
JH
Kim
Sung Hyun
SH
Park
Chul-Seung
CS
Kim
Eunjoon
E
Song
Woo Keun
WK
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000737:chemistry; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D049229:Dendritic Spines / Q000502:physiology* / Q000648:ultrastructure*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D013569:Synapses / Q000502:physiology; D014162:Transfection
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C512412:SHANK1 protein, mouse; C542056:SPIN90 protein, mouse; D005982:Glutathione Transferase