Regulation of dendritic spine morphology by SPIN90, a novel Shank binding partner

• Published in: Journal of neurochemistry 2009-05, Vol.109 (4), p.1106-1117
• Main Authors: Kim, Seon‐Myung, Choi, Kyu Yeong, Cho, In Ha, Rhy, Jin Hee, Kim, Sung Hyun, Park, Chul‐Seung, Kim, Eunjoon, Song, Woo Keun
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - physiology; Aminoacid receptors (glycine, glutamate, gaba); Animals; Binding Sites; Biological and medical sciences; Blotting, Western; Brain; Brain Chemistry - physiology; Cell Line, Tumor; Cell receptors; Cell structures and functions; Cells, Cultured; cytoskeleton; Cytoskeleton - chemistry; Cytoskeleton, cytoplasm. Intracellular movements; dendritic spines; Dendritic Spines - physiology; Dendritic Spines - ultrastructure; DNA, Complementary - biosynthesis; DNA, Complementary - genetics; Fundamental and applied biological sciences. Psychology; Glutathione Transferase - metabolism; hippocampus; Humans; Immunohistochemistry; Immunoprecipitation; Membrane Proteins - genetics; Membrane Proteins - physiology; Mice; Mice, Knockout; Molecular and cellular biology; Morphology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - physiology; Nervous system; Plasmids - genetics; postsynaptic density; Protein Binding; Proteins; Rodents; scaffolding protein; Synapses - physiology; Transfection
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2009.06039.x

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.