nesh regulates dendritic spine morphology and synapse formation粉状的调节树突棘突触形态和形成.pdfVIP

NESH Regulates Dendritic Spine Morphology and Synapse Formation 1 2 1 3 1 Jeomil Bae , Bong Hwan Sung , In Ha Cho , Seon-Myung Kim , Woo Keun Song * 1 Cell Dynamics and Bioimaging Research Center, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea, 2 Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America, 3 Department of Cell Biology and Neurology, Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, Georgia, United States of America Abstract Background: Dendritic spines are small membranous protrusions on the neuronal dendrites that receive synaptic input from axon terminals. Despite their importance for integrating the enormous information flow in the brain, the molecular mechanisms regulating spine morphogenesis are not well understood. NESH/Abi-3 is a member of the Abl interactor (Abi) protein family, and its overexpression is known to reduce cell motility and tumor metastasis. NESH is prominently expressed in the brain, but its function there remains unknown. Methodology/Principal Findings: NESH was strongly expressed in the hippocampus and moderately expressed in the cerebral cortex, cerebellum and striatum, where it co-localized with the postsynaptic proteins PSD95, SPIN90 and F-actin in dendritic spines. Overexpression of NESH reduced numbers of mushroom-type spines and synapse density but increased thin, filopodia-like spines and had no effect on spine density. siRNA knockdown of NESH also reduced mushroom spine numbers and inhibited synapse formation but it increased spine density. The N-terminal region of NESH co-sedimented with filamentous actin (F-actin), which is an essential component of dend