DCX

Official Full Name

doublecortin

Organism

Homo sapiens

GeneID

1641

Background

This gene encodes a member of the doublecortin family. The protein encoded by this gene is a cytoplasmic protein and contains two doublecortin domains, which bind microtubules. In the developing cortex, cortical neurons must migrate over long distances to reach the site of their final differentiation. The encoded protein appears to direct neuronal migration by regulating the organization and stability of microtubules. In addition, the encoded protein interacts with LIS1, the regulatory gamma subunit of platelet activating factor acetylhydrolase, and this interaction is important to proper microtubule function in the developing cortex. Mutations in this gene cause abnormal migration of neurons during development and disrupt the layering of the cortex, leading to epilepsy, cognitive disability, subcortical band heterotopia ("double cortex" syndrome) in females and lissencephaly ("smooth brain" syndrome) in males. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2010]

Synonyms

DC; DBCN; LISX; SCLH; XLIS;

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Detailed Information

The doublecortin (DCX) gene is an essential regulator of brain development and function. It is highly conserved across species and is involved in various cellular processes, including neuronal migration, synaptic plasticity, and axonal growth.

Structure and Expression of DCX

The DCX gene is located on the X-chromosome and encodes a protein of 165-175 kDa. The protein consists of four main domains: an N-terminal leucine-rich domain, a central glutamic acid-rich domain, a C-terminal domain containing a pair of leucine zippers, and a proline-rich domain. The DCX protein is primarily expressed in the brain, specifically in the dentate gyrus, hippocampus, and cerebral cortex.

Function of DCX

The primary function of the DCX gene is to regulate neuronal migration during brain development. It does so by interacting with various cellular components, including microtubules and actin filaments. The DCX protein plays a crucial role in the formation of neural circuits, as it promotes the migration of neurons to their proper positions in the developing brain. Additionally, DCX has been shown to regulate synaptic plasticity and axonal growth, which are essential for proper neural function.

DCX Singal pathway

The Doublecortin (DCX) gene is a key regulator in the signaling pathway of neuronal migration and development. It encodes a protein that promotes the migration of neurons by interacting with multiple signaling pathways, including the Wnt, RTK/Ras/MAPK, and Notch pathways. DCX also plays a crucial role in the formation of neuronal circuits, as it regulates the differentiation and migration of neurons during brain development. Moreover, mutations in the DCX gene are associated with various neurological disorders, highlighting the importance of understanding its signaling pathway for therapeutic interventions.

Figure 1. Schematic diagram shows that DCX facilitates the extension of the somatic Golgi complex into dendrite through MT-associated proteins and motors

Implications of DCX in Disease

Alterations in the expression or function of the DCX gene can have significant implications for human health, as they can disrupt normal neural development and function. mutations in the DCX gene have been associated with various neurological disorders, including X-linked lissencephaly-mental retardation syndrome (XLMRS), a severe developmental disorder characterized by abnormal brain structure and cognitive impairment. Furthermore, reduced DCX expression has been observed in several neurodegenerative diseases, such as Alzheimer's disease and Huntington's disease, suggesting a potential role in the pathophysiology of these disorders.

Overexpression of the DCX gene can also have detrimental effects, as it has been associated with increased neuronal migration and plasticity, which may contribute to the development of epilepsy and other neurological disorders. Therefore, understanding the regulation of DCX expression and function is crucial for developing therapeutic interventions targeting these disorders.

References:

Rafiei, Atefeh et al. "Doublecortin engages the microtubule lattice through a cooperative binding mode involving its C-terminal domain." eLife vol. 11 e66975. 29 Apr. 2022, doi:10.7554/eLife.66975
Li, Peijun et al. "Doublecortin facilitates the elongation of the somatic Golgi apparatus into proximal dendrites." Molecular biology of the cell vol. 32,5 (2021): 422-434. doi:10.1091/mbc.E19-09-0530

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