Disease relevance of Dclk1

• In cultured cortical neural progenitors, DCLK RNAi Lentivirus disrupts the structure of mitotic spindles and the progression of M phase, causing an increase of cell-cycle exit index and an ectopic commitment to a neuronal fate [1].

High impact information on Dclk1

• A second locus, doublecortin-like kinase (Dclk), encodes a protein with similar "doublecortin domains" and microtubule stabilization properties that may compensate for Dcx [2].
• Dcx and Dclk may directly or indirectly regulate microtubule-based vesicle transport, a process critical to both neuronal migration and axon outgrowth [2].
• Through a dynein-dependent mechanism, DCLK regulates the formation of bipolar mitotic spindles and the proper transition from prometaphase to metaphase during mitosis [1].
• Dcx/Dclk-deficient dissociated neurons show abnormal axon outgrowth and dendritic structure, with defects in axonal transport of synaptic vesicle proteins [2].
• The isolated kinase domain retains catalytic activity and is structurally similar to CPG16, a second product of the DCLK gene expressed in the adult brain that lacks the doublecortin domain [3].

Biological context of Dclk1

• 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 [4].

Anatomical context of Dclk1

• Immunolocalization studies in COS7 and NIH-3T3 cells showed mostly cytoplasmic localization of CPG16 that turned partially nuclear upon stimulation with 8-bromo-cAMP [5].

Associations of Dclk1 with chemical compounds

• Of great interest is the effect of melatonin upon the expression of a large number of genes related to calcium exchange, such as Cul5, Dcamkl1 and Kcnn4; a significant effect of melatonin on the expression of some oncogenesis-related genes was also detected [6].
• Here we report that DCLK is a physiological substrate for the cysteine protease calpain [3].
• Here, we describe the expression and characterization of candidate plasticity gene 16 (cpg16), a protein serine/threonine kinase that was previously isolated from rat hippocampus as a plasticity-related gene [5].
• CPG16, a novel protein serine/threonine kinase downstream of cAMP-dependent protein kinase [5].

Regulatory relationships of Dclk1

• We propose that in neurons cleavage of DCLK by calpain represents a calcium responsive mechanism to regulate localization of the DCLK kinase domain [3].
• Although the stimulation of CPG16 activity was inhibited by the cAMP-dependent protein kinase inhibitor H-89, it did not serve as a direct substrate for this kinase [5].

Other interactions of Dclk1

• DCLK consists of an N-terminal doublecortin domain, responsible for its localization to microtubules, and a C-terminal serine-threonine kinase domain [3].
• Cleavage of DCLK by calpain severs the kinase domain from its microtubule anchorage domain and releases it into the cytoplasm [3].

References