title: NESH regulates dendritic spine morphology and synapse formation.
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.
  
  
  RESULTS
  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 dendritic spines, suggesting this interaction is important for the maturation of dendritic spines.
  
  
  CONCLUSIONS
  NESH is a novel F-actin binding protein that likely plays important roles in the regulation of dendritic spine morphogenesis and synapse formation.
authors.affiliation: Cell Dynamics and Bioimaging Research Center, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Jeomil
authors.initials: J
authors.lastname: Bae
authors.forename: Bong Hwan
authors.initials: BH
authors.lastname: Sung
authors.forename: In Ha
authors.initials: IH
authors.lastname: Cho
authors.forename: Seon-Myung
authors.initials: SM
authors.lastname: Kim
authors.forename: Woo Keun
authors.initials: WK
authors.lastname: Song
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D048430:Cell Shape; D049229:Dendritic Spines / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
chemical_list: C573793:Abi3 protein, rat; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins