High impact information on DCLK1

• We here report a solution structure of the N-terminal DCX domain of human doublecortin and a 1.5 A resolution crystal structure of the equivalent domain from human DCLK [1].
• DCX tandems are found in doublecortin, a 360-residue protein expressed in migrating neurons; the doublecortin-like kinase (DCLK); the product of the RP1 gene that is responsible for a form of inherited blindness; and several other proteins [1].
• Here we identified DC and KI in the brains of human and rat fetuses by immunochemical and immunohistochemical means [2].
• Targeted deletion of Dclk shows no appreciable developmental defect in the hippocampus, but removal of both genes shows severe hippocampal lamination defects involving the entire cornu ammonis and dentate gyrus fields that mimic the human phenotype [3].
• Ectopic expression of DCLK in COS cells results in colocalization with microtubules, and phosphorylated DCLK copurifies with microtubules during assembly from embryonic brain extract [4].

Biological context of DCLK1

• Northern analysis detected three major transcript isoforms of the DCAMKL1 gene expressed differentially and predominantly in human fetal and adult brain and during mouse embryogenesis (11-17 dpc) [5].
• Human KIAA0369 was mapped by fluorescence in situ hybridization (FISH) to chromosome 13q13-q14 [6].
• We conclude that alternative splicing of the DCAMKL gene may generate different but similar proteins in the adult rat hippocampus thereby regulating different but overlapping aspects of DCAMKL controlled neuronal plasticity [7].

Anatomical context of DCLK1

• Immunostaining of the developing neocortex disclosed localization of DC and KI immunoreactivities in neuronal cell bodies and processes in the zones of ongoing neuronal migration [2].
• We demonstrate that DCLK is a microtubule-associated active protein kinase expressed in growth cones of postmitotic neurons [4].
• In the adult brain, KIAA0369 was expressed in all 15 different regions examined, more intensely in cerebral cortex, occipital pole, frontal lobe, amygdala, and hippocampus, and less intensely in corpus callosum and thalamus [6].

Regulatory relationships of DCLK1

• During brain development DCLK is expressed mainly in postmigratory neurons in a similar pattern to DCX [4].

Other interactions of DCLK1

• These results and its homology with the DCX and Ca2+/calmodulin dependent kinase proteins suggest a likely role for DCAMKL1 transmembrane protein in developing and adult brain, possibly in a pathway of cortical development [5].

Analytical, diagnostic and therapeutic context of DCLK1

• In this study, Western blotting demonstrated that both DC and KI are specific to the nervous system and are abundant during the fetal period, around 20 gestational weeks in humans and embryonic days 17 to 20 in rats [2].
• Here, the expression and purification of the tandem from human DCLK (residues 49-280) and of the isolated domains (residues 49-154 and 176-280) and the successful crystallization of the N-terminal domain (N-DCLK) are reported [8].

References