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DPP6 regulation of dendritic morphogenesis impacts hippocampal synaptic development.

Nature communications | Aug 5, 2013

Dipeptidyl-peptidase 6 is an auxiliary subunit of Kv4-mediated A-type K(+) channels that, in addition to enhancing channel surface expression, potently accelerates their kinetics. The dipeptidyl-peptidase 6 gene has been associated with a number of human central nervous system disorders including autism spectrum disorders and schizophrenia. Here we employ knockdown and genetic deletion of dipeptidyl-peptidase 6 to reveal its importance for the formation and stability of dendritic filopodia during early neuronal development. We find that the hippocampal neurons lacking dipeptidyl-peptidase 6 show a sparser dendritic branching pattern along with fewer spines throughout development and into adulthood. In electrophysiological and imaging experiments, we show that these deficits lead to fewer functional synapses and occur independently of the potassium channel subunit Kv4.2. We report that dipeptidyl-peptidase 6 interacts with a filopodia-associated myosin as well as with fibronectin in the extracellular matrix. dipeptidyl-peptidase 6 therefore has an unexpected but important role in cell adhesion and motility, impacting the hippocampal synaptic development and function.

Pubmed ID: 23912628 RIS Download

Mesh terms: Animals | CA1 Region, Hippocampal | Cell Adhesion | Dendrites | Dendritic Spines | Dipeptidyl-Peptidases and Tripeptidyl-Peptidases | Extracellular Matrix | Fibronectins | Gene Knockdown Techniques | Hippocampus | Humans | Immunoprecipitation | Mice | Mice, Knockout | Morphogenesis | Protein Binding | Pseudopodia | Rats | Rats, Sprague-Dawley | Shal Potassium Channels | Synapses

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Associated grants

  • Agency: NINDS NIH HHS, Id: NS045217
  • Agency: NIDCD NIH HHS, Id: R01DC03299
  • Agency: NIDCD NIH HHS, Id: R01 DC003299
  • Agency: NINDS NIH HHS, Id: R01 NS030989
  • Agency: NINDS NIH HHS, Id: R01 NS045217

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Software tool for automated microscope acquisition, device control, and image analysis. Used for integrating dissimilar fluorescent microscope hardware and peripherals into a single custom workstation, while providing all the tools needed to perform analysis of acquired images. Offers user friendly application modules for analysis such as cell signaling, cell counting, and protein expression.


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