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Related Experiment Video

Updated: Mar 23, 2026

Genetic Manipulation of Cerebellar Granule Neurons In Vitro and In Vivo to Study Neuronal Morphology and Migration
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CUB and Sushi multiple domains 3 regulates dendrite development.

Tomoharu Mizukami1, Takao Kohno1, Mitsuharu Hattori1

  • 1Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.

Neuroscience Research
|April 2, 2016
PubMed
Summary

Mutations in the CUB and Sushi multiple domains 3 (CSMD3) gene are linked to psychiatric disorders. This study reveals CSMD3 regulates neuronal dendrite development, suggesting its malfunction contributes to these conditions.

Keywords:
CSMD3NeuronPsychiatric disorder

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • CUB and Sushi multiple domains 3 (CSMD3) is a large protein found in the brain.
  • CSMD3 gene mutations are associated with schizophrenia and autism.
  • The protein's biochemical properties and functions were previously unknown.

Purpose of the Study:

  • To investigate the biochemical properties and cellular functions of the CSMD3 protein.
  • To determine the role of CSMD3 in neuronal development, particularly dendritic morphology.
  • To explore the potential link between CSMD3 dysfunction and psychiatric disorders.

Main Methods:

  • Immunohistochemistry to determine CSMD3 localization in neurons.
  • Cell culture of hippocampal neurons to study CSMD3 expression and function.
  • Overexpression studies to assess the impact of CSMD3 on dendritic branching.
  • Analysis of CSMD3's extracellular and intracellular regions to identify functional domains.

Main Results:

  • CSMD3 is an oligomeric type I transmembrane protein localized in the apical dendrites of hippocampal pyramidal neurons.
  • CSMD3 expression in cultured neurons begins after 7 days in vitro.
  • Overexpression of CSMD3 significantly increased dendritic branching in hippocampal neurons.
  • The extracellular region of CSMD3 is essential for regulating dendritic morphology, while the intracellular region is not.

Conclusions:

  • CSMD3 plays a crucial role in regulating dendritic development in the postnatal brain.
  • CSMD3 may function as a co-receptor for an unknown membrane protein involved in dendrite formation.
  • Dysfunctional CSMD3 is implicated as a potential factor in the pathogenesis of psychiatric disorders like schizophrenia and autism.