Traffic of Kv4 K+ channels mediated by KChIP1 is via a novel post-ER vesicular pathway.
The traffic of Kv4 K+ channels is regulated by the potassium channel interacting proteins (KChIPs). Kv4.2 expressed alone was not retained within the ER, but reached the Golgi complex. Coexpression of KChIP1 resulted in traffic of the channel to the plasma membrane, and traffic was abolished when mutations were introduced into the EF-hands with channel captured on vesicular structures that colocalized with KChIP1(2-4)-EYFP. The EF-hand mutant had no effect on general exocytic traffic. Traffic of Kv4.2 was coat protein complex I (COPI)-dependent, but KChIP1-containing vesicles were not COPII-coated, and expression of a GTP-loaded Sar1 mutant to block COPII function more effectively inhibited traffic of vesicular stomatitis virus glycoprotein (VSVG) than did KChIP1/Kv4.2 through the secretory pathway. Therefore, KChIP1seems to be targeted to post-ER transport vesicles, different from COPII-coated vesicles and those involved in traffic of VSVG. When expressed in hippocampal neurons, KChIP1 co-distributed with dendritic Golgi outposts; therefore, the KChIP1 pathway could play an important role in local vesicular traffic in neurons.
Hasdemir
Burcu
B
The Physiological Laboratory, School of Biomedical Sciences, University of Liverpool, Liverpool L69 3BX, England, UK.
Fitzgerald
Daniel J
DJ
Prior
Ian A
IA
Tepikin
Alexei V
AV
Burgoyne
Robert D
RD
D000818:Animals; D022181:COP-Coated Vesicles / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D020755:Coat Protein Complex I / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051605:Kv Channel-Interacting Proteins / Q000502:physiology*; D008297:Male; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D051672:Shal Potassium Channels / Q000378:metabolism / Q000502:physiology*; D014721:Vesicular stomatitis Indiana virus; D014764:Viral Proteins / Q000378:metabolism
D020755:Coat Protein Complex I; D051605:Kv Channel-Interacting Proteins; D051672:Shal Potassium Channels; D014764:Viral Proteins; C493083:SAR1A protein, human; C513282:SAR1B protein, human; D020559:Monomeric GTP-Binding Proteins; D002118:Calcium