DPP10 splice variants are localized in distinct neuronal populations and act to differentially regulate the inactivation properties of Kv4-based ion channels.
Dipeptidyl peptidase-like proteins (DPLs) and Kv-channel-interacting proteins (KChIPs) join Kv4 pore-forming subunits to form multi-protein complexes that underlie subthreshold A-type currents (I(SA)) in neuronal somatodendritic compartments. Here, we characterize the functional effects and brain distributions of N-terminal variants belonging to the DPL dipeptidyl peptidase 10 (DPP10). In the Kv4.2+KChIP3+DPP10 channel complex, all DPP10 variants accelerate channel gating kinetics; however, the splice variant DPP10a produces uniquely fast inactivation kinetics that accelerates with increasing depolarization. This DPP10a-specific inactivation dominates in co-expression studies with KChIP4a and other DPP10 isoforms. Real-time qRT-PCR and in situ hybridization analyses reveal differential expression of DPP10 variants in rat brain. DPP10a transcripts are prominently expressed in the cortex, whereas DPP10c and DPP10d mRNAs exhibit more diffuse distributions. Our results suggest that DPP10a underlies rapid inactivation of cortical I(SA), and the regulation of isoform expression may contribute to the variable inactivation properties of I(SA) across different brain regions.
Jerng
Henry H
HH
Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza, S630 Houston, TX 77030, USA. hjerng@cns.bcm.tmc.edu
Lauver
Aaron D
AD
Pfaffinger
Paul J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D015640:Ion Channel Gating; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D007527:Isoenzymes; D051605:Kv Channel-Interacting Proteins; D021122:Protein Subunits; D051672:Shal Potassium Channels; C476879:DPP10 protein, human; C523849:DPP10 protein, rat; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases