Doublecortin

Neuronal migration protein doublecortin, also known as doublin or lissencephalin-X is a is_associated_with::protein that in humans is encoded by the DCX is_associated_with::gene.

Function
Doublecortin (DCX) is a is_associated_with::microtubule-associated protein expressed by neuronal precursor cells and immature is_associated_with::neurons in embryonic and adult cortical structures. Neuronal precursor cells begin to express DCX while actively dividing, and their neuronal daughter cells continue to express DCX for 2–3 weeks as the cells mature into neurons. Downregulation of DCX begins after 2 weeks, and occurs at the same time that these cells begin to express, is_associated_with::NeuN, a marker for mature neurons.

Due to the nearly exclusive expression of DCX in developing neurons, this is_associated_with::protein has been used increasingly as a marker for is_associated_with::neurogenesis. Indeed, the levels of DCX expression increase in response to exercise, which occurs in parallel with increased is_associated_with::BrdU labelling, currently a "gold standard" in measuring neurogenesis.

Doublecortin was found to bind to the is_associated_with::microtubule is_associated_with::cytoskeleton. is_associated_with::In vivo and is_associated_with::in vitro assays show that Doublecortin stabilises microtubules and causes bundling. Doublecortin is a basic is_associated_with::protein with an is_associated_with::iso-electric point of 10, typical of microtubule-binding is_associated_with::proteins.

Structure
The detailed is_associated_with::sequence analysis of Doublecortin and Doublecortin-like proteins allowed the identification of an tandem repeat of evolutionarily conserved Doublecortin (DC) domains. These domains are found in the is_associated_with::N terminus of proteins and consists of tandemly repeated copies of an around 80 is_associated_with::amino acids region. It has been suggested that the first DC domain of Doublecortin binds is_associated_with::tubulin and enhances microtubule polymerisation.

Doublecortin has been shown to influence the structure of microtubules. Microtubule nucleated in vitro in the presence of Doublecortin have almost exclusively 13 protofilaments, whereas microtubule nucleated without Doublecortin are present in a range of different sizes.

Interactions
Doublecortin has been shown to interact with is_associated_with::PAFAH1B1.

Clinical significance
Doublecortin is mutated in X-linked is_associated_with::lissencephaly and the double cortex syndrome, and the clinical manifestations are sex-linked. In males, X-linked lissencephaly produces a smooth brain due to lack of migration of immature neurons, without normal folding of the brain surface. Double cortex syndrome is characterized by abnormal migration of neural tissue during development which results in two bands of misplaced neurons within the subcortical white, generating two cortices, giving the name to the syndrome; this finding generally occurs in females. The mutation was discovered by is_associated_with::Joseph Gleeson and is_associated_with::Christopher A. Walsh in Boston.