The CD26-related dipeptidyl aminopeptidase-like protein DPPX is a critical component of neuronal A-type K+ channels.
Subthreshold-activating somatodendritic A-type potassium channels have fundamental roles in neuronal signaling and plasticity which depend on their unique cellular localization, voltage dependence, and kinetic properties. Some of the components of A-type K(+) channels have been identified; however, these do not reproduce the properties of the native channels, indicating that key molecular factors have yet to be unveiled. We purified A-type K(+) channel complexes from rat brain membranes and found that DPPX, a protein of unknown function that is structurally related to the dipeptidyl aminopeptidase and cell adhesion protein CD26, is a novel component of A-type K(+) channels. DPPX associates with the channels' pore-forming subunits, facilitates their trafficking and membrane targeting, reconstitutes the properties of the native channels in heterologous expression systems, and is coexpressed with the pore-forming subunits in the somatodendritic compartment of CNS neurons.
Nadal
Marcela S
MS
Department of Physiology and Neuroscience and Department of Biochemistry, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Ozaita
Andrés
A
Amarillo
Yimy
Y
Vega-Saenz de Miera
Eleazar
E
Ma
Yuliang
Y
Mo
Wenjun
W
Goldberg
Ethan M
EM
Misumi
Yoshio
Y
Ikehara
Yukio
Y
Neubert
Thomas A
TA
Rudy
Bernardo
B
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002531:Cerebellum / Q000166:cytology; D003712:Dendrites / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D005109:Extracellular Matrix / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology* / Q000648:ultrastructure; D009865:Oocytes / Q000502:physiology; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011233:Precipitin Tests; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051672:Shal Potassium Channels; D014981:Xenopus
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels; C557320:DPP6 protein, rat; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4