Limits...
Doublecortin-like kinase enhances dendritic remodelling and negatively regulates synapse maturation.

Shin E, Kashiwagi Y, Kuriu T, Iwasaki H, Tanaka T, Koizumi H, Gleeson JG, Okabe S - Nat Commun (2013)

Bottom Line: Here we report two distinct functions of doublecortin-like kinases, chimeric proteins containing both a microtubule-binding domain and a kinase domain in postmitotic neurons.First, doublecortin-like kinases localize to the distal dendrites and promote their growth by enhancing microtubule bundling.Thus, doublecortin-like kinases are critical regulators of dendritic development by means of their specific targeting to the distal dendrites, and their local control of dendritic growth and synapse maturation.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular Neurobiology, University of Tokyo, Tokyo 113-0033, Japan.

ABSTRACT
Dendritic morphogenesis and formation of synapses at appropriate dendritic locations are essential for the establishment of proper neuronal connectivity. Recent imaging studies provide evidence for stabilization of dynamic distal branches of dendrites by the addition of new synapses. However, molecules involved in both dendritic growth and suppression of synapse maturation remain to be identified. Here we report two distinct functions of doublecortin-like kinases, chimeric proteins containing both a microtubule-binding domain and a kinase domain in postmitotic neurons. First, doublecortin-like kinases localize to the distal dendrites and promote their growth by enhancing microtubule bundling. Second, doublecortin-like kinases suppress maturation of synapses through multiple pathways, including reduction of PSD-95 by the kinase domain and suppression of spine structural maturation by the microtubule-binding domain. Thus, doublecortin-like kinases are critical regulators of dendritic development by means of their specific targeting to the distal dendrites, and their local control of dendritic growth and synapse maturation.

Show MeSH

Related in: MedlinePlus

Regulation of AMPA receptor-mediated current by DCLK1(a–e) mEPSC traces (a). Scale bar, 20 pA, 300 ms. The average and cumulative distribution of mEPSC amplitudes (b,d) and inter-event intervals (c,e) recorded from dissociated hippocampal neurons. Overexpression of DCLK1-GFP by infection of recombinant adenoviruses induced a decrease in mEPSC amplitudes and increase in inter-event intervals. (GFP: n = 6 cells and DCLK1-GFP: n = 8 cells; one-way analysis of variance (ANOVA): *P<0.05, **P<0.01.) (f) Traces of evoked EPSCs from neurons expressing either GFP only or DCLK1-GFP by using recombinant adenoviruses. Scale bar, 50 pA, 50 ms. (g) Mean and s.e.m of the AMPA/NMDA EPSC ratio in neurons overexpressing GFP alone or DCLK1-GFP. The graph shows significant suppression of the AMPA/NMDA EPSC ratio by DCLK1-GFP overexpression (GFP: n = 8 cells and DCLK1-GFP: n = 11 cells; one-way ANOVA: *P<0.05). All numeric data are given as mean ± s.e.m.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4017031&req=5

Figure 6: Regulation of AMPA receptor-mediated current by DCLK1(a–e) mEPSC traces (a). Scale bar, 20 pA, 300 ms. The average and cumulative distribution of mEPSC amplitudes (b,d) and inter-event intervals (c,e) recorded from dissociated hippocampal neurons. Overexpression of DCLK1-GFP by infection of recombinant adenoviruses induced a decrease in mEPSC amplitudes and increase in inter-event intervals. (GFP: n = 6 cells and DCLK1-GFP: n = 8 cells; one-way analysis of variance (ANOVA): *P<0.05, **P<0.01.) (f) Traces of evoked EPSCs from neurons expressing either GFP only or DCLK1-GFP by using recombinant adenoviruses. Scale bar, 50 pA, 50 ms. (g) Mean and s.e.m of the AMPA/NMDA EPSC ratio in neurons overexpressing GFP alone or DCLK1-GFP. The graph shows significant suppression of the AMPA/NMDA EPSC ratio by DCLK1-GFP overexpression (GFP: n = 8 cells and DCLK1-GFP: n = 11 cells; one-way ANOVA: *P<0.05). All numeric data are given as mean ± s.e.m.

Mentions: The exogenous overexpression of DCLK1-GFP caused a reduction in the synaptic content of PSD-95 and morphological alteration of spines. We next evaluated the effect of DCLK1 overexpression on synaptic transmission by recording miniature excitatory post-synaptic currents (mEPSCs) from DCLK1-GFP-overexpressing neurons (Fig. 6a). The amplitude of mEPSCs was decreased in neurons expressing DCLK1-GFP (Fig. 6b,d) and the inter-event interval was increased (Fig. 6c,e).


Doublecortin-like kinase enhances dendritic remodelling and negatively regulates synapse maturation.

Shin E, Kashiwagi Y, Kuriu T, Iwasaki H, Tanaka T, Koizumi H, Gleeson JG, Okabe S - Nat Commun (2013)

Regulation of AMPA receptor-mediated current by DCLK1(a–e) mEPSC traces (a). Scale bar, 20 pA, 300 ms. The average and cumulative distribution of mEPSC amplitudes (b,d) and inter-event intervals (c,e) recorded from dissociated hippocampal neurons. Overexpression of DCLK1-GFP by infection of recombinant adenoviruses induced a decrease in mEPSC amplitudes and increase in inter-event intervals. (GFP: n = 6 cells and DCLK1-GFP: n = 8 cells; one-way analysis of variance (ANOVA): *P<0.05, **P<0.01.) (f) Traces of evoked EPSCs from neurons expressing either GFP only or DCLK1-GFP by using recombinant adenoviruses. Scale bar, 50 pA, 50 ms. (g) Mean and s.e.m of the AMPA/NMDA EPSC ratio in neurons overexpressing GFP alone or DCLK1-GFP. The graph shows significant suppression of the AMPA/NMDA EPSC ratio by DCLK1-GFP overexpression (GFP: n = 8 cells and DCLK1-GFP: n = 11 cells; one-way ANOVA: *P<0.05). All numeric data are given as mean ± s.e.m.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4017031&req=5

Figure 6: Regulation of AMPA receptor-mediated current by DCLK1(a–e) mEPSC traces (a). Scale bar, 20 pA, 300 ms. The average and cumulative distribution of mEPSC amplitudes (b,d) and inter-event intervals (c,e) recorded from dissociated hippocampal neurons. Overexpression of DCLK1-GFP by infection of recombinant adenoviruses induced a decrease in mEPSC amplitudes and increase in inter-event intervals. (GFP: n = 6 cells and DCLK1-GFP: n = 8 cells; one-way analysis of variance (ANOVA): *P<0.05, **P<0.01.) (f) Traces of evoked EPSCs from neurons expressing either GFP only or DCLK1-GFP by using recombinant adenoviruses. Scale bar, 50 pA, 50 ms. (g) Mean and s.e.m of the AMPA/NMDA EPSC ratio in neurons overexpressing GFP alone or DCLK1-GFP. The graph shows significant suppression of the AMPA/NMDA EPSC ratio by DCLK1-GFP overexpression (GFP: n = 8 cells and DCLK1-GFP: n = 11 cells; one-way ANOVA: *P<0.05). All numeric data are given as mean ± s.e.m.
Mentions: The exogenous overexpression of DCLK1-GFP caused a reduction in the synaptic content of PSD-95 and morphological alteration of spines. We next evaluated the effect of DCLK1 overexpression on synaptic transmission by recording miniature excitatory post-synaptic currents (mEPSCs) from DCLK1-GFP-overexpressing neurons (Fig. 6a). The amplitude of mEPSCs was decreased in neurons expressing DCLK1-GFP (Fig. 6b,d) and the inter-event interval was increased (Fig. 6c,e).

Bottom Line: Here we report two distinct functions of doublecortin-like kinases, chimeric proteins containing both a microtubule-binding domain and a kinase domain in postmitotic neurons.First, doublecortin-like kinases localize to the distal dendrites and promote their growth by enhancing microtubule bundling.Thus, doublecortin-like kinases are critical regulators of dendritic development by means of their specific targeting to the distal dendrites, and their local control of dendritic growth and synapse maturation.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular Neurobiology, University of Tokyo, Tokyo 113-0033, Japan.

ABSTRACT
Dendritic morphogenesis and formation of synapses at appropriate dendritic locations are essential for the establishment of proper neuronal connectivity. Recent imaging studies provide evidence for stabilization of dynamic distal branches of dendrites by the addition of new synapses. However, molecules involved in both dendritic growth and suppression of synapse maturation remain to be identified. Here we report two distinct functions of doublecortin-like kinases, chimeric proteins containing both a microtubule-binding domain and a kinase domain in postmitotic neurons. First, doublecortin-like kinases localize to the distal dendrites and promote their growth by enhancing microtubule bundling. Second, doublecortin-like kinases suppress maturation of synapses through multiple pathways, including reduction of PSD-95 by the kinase domain and suppression of spine structural maturation by the microtubule-binding domain. Thus, doublecortin-like kinases are critical regulators of dendritic development by means of their specific targeting to the distal dendrites, and their local control of dendritic growth and synapse maturation.

Show MeSH
Related in: MedlinePlus