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SynCAMs in Normal Vertebrate Neural Development and Neuropsychiatric Disorders: from the Perspective of the OCAs

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Abstract

Neuronal synaptic junctions connect neurons to enable neuronal signal transmission in the nervous system. The proper establishment of synaptic connections required many adhesion molecules. Malfunctions of these adhesion molecules can result in neural development disorders and neuropsychiatric disorders. How specific synapses are established by various adhesion molecules for proper neural circuitry is a fundamental question of neuroscience. SynCAMs, also named CADMs, Necl, etc., are among the many adhesion proteins found in synapses. Here, we review the current understanding of the physical properties of SynCAMs and their roles in axon pathfinding, myelination, synaptogenesis, and synaptic plasticity. In addition, we discuss the involvement of SynCAMs in neuropsychiatric disorders. Finally, we propose that SynCAM functions can be better viewed and understood from the perspective of orientational cell adhesions (OCAs). In particular, we discuss the possibilities of how SynCAMs can be regulated at the cell-type specific expression, transcription variants, posttranslational modification, and subcellular localization to modulate the diversity of SynCAMs as OCA molecules. Being major components of the synapses, SynCAMs continue to be an important research topic of neuroscience, and many outstanding questions are waiting to be answered.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding authors on reasonable request.

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Funding

L. Zhang was supported by the Department of Psychology at Dalian Medical University. X. Wei was supported by the Department of Ophthalmology at the University of Pittsburgh, the Eye and Ear Foundation of Pittsburgh, and an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology at the University of Pittsburgh.

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  1. Department of Psychology, Dalian Medical University, Dalian, China

    Lili Zhang

  2. Departments of Ophthalmology, Developmental Biology, and Microbiology & Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA

    Xiangyun Wei

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Lili Zhang and Xiangyun Wei contributed to literature review and analysis, conceptualization of the review scope, and the initial draft of the manuscript. Xiangyun Wei revised and edited the final version. Both authors approved the final manuscript.

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Correspondence to Lili Zhang or Xiangyun Wei.

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Zhang, L., Wei, X. SynCAMs in Normal Vertebrate Neural Development and Neuropsychiatric Disorders: from the Perspective of the OCAs. Mol Neurobiol 61, 358–371 (2024). https://doi.org/10.1007/s12035-023-03579-2

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