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Impaired glycosylation blocks DPP10 cell surface expression and alters the electrophysiology of i to channel complex

Cotella, Diego
•
Radicke, Susanne
•
Bortoluzzi, Alessio
altro
SBLATTERO, DANIELE
2010
  • journal article

Periodico
PFLÜGERS ARCHIV
Abstract
DPP10 is a transmembrane glycosylated protein belonging to the family of dipeptidyl aminopeptidase-like proteins (DPPLs). DPPLs are auxiliary subunits involved in the regulation of voltage-gated Kv4 channels, key determinants of cardiac and neuronal excitability. Although it is known that DPPLs are needed to generate native-like currents in heterologous expression systems, the molecular basis of this involvement are still poorly defined. In this study, we investigated the functional relevance of DPP10 glycosylation in modulating Kv4.3 channel activities. Using transfected Chinese hamster ovary (CHO) cells to reconstitute Kv4 complex, we show that the pharmacological inhibition of DPP10 glycosylation by tunicamycin and neuraminidase affects transient outward potassium current (I (to)) kinetics. Tunicamycin completely blocked DPP10 glycosylation and reduced DPP10 cell surface expression. The accelerating effects of DPP10 on Kv4.3 current kinetics, i.e. on inactivation and recovery from inactivation, were abolished. Neuraminidase produced different effects on current kinetics than tunicamycin, i.e., shifted the voltage dependence to more negative potentials. The effects of tunicamycin on the native I (to) currents of human atrial myocytes expressing DPP10 were similar to those of the KV4.3/KChIP2/DPP10 complex in CHO cells. Our results suggest that N-linked glycosylation of DPP10 plays an important role in modulating Kv4 channel activities.
DOI
10.1007/s00424-010-0824-2
WOS
WOS:000277791100008
SCOPUS
2-s2.0-77952889614
Archivio
http://hdl.handle.net/11368/2857184
Diritti
metadata only access
Soggetti
  • DPP10 protein

  • Electrophysiology

  • Glycosylation

  • KChIP2 protein

  • Kv4.3 potassium chann...

  • Tunicamycin

  • Animals

  • CHO Cells

  • Cell Membrane

  • Cricetinae

  • Cricetulus

  • Dipeptidyl-Peptidases...

  • Glycosylation

  • Heart Atria

  • Humans

  • Kinetics

  • Kv Channel-Interactin...

  • Membrane Potentials

  • Myocytes, Cardiac

  • Neuraminidase

  • Potassium

  • Protein Transport

  • Shal Potassium Channe...

  • Transfection

  • Tunicamycin

  • Ion Channel Gating

  • Protein Processing, P...

  • Physiology

  • Clinical Biochemistry...

  • Physiology (medical)

Web of Science© citazioni
13
Data di acquisizione
Jun 12, 2022
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