Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4.
Presenilin (PS) genes linked to early-onset familial Alzheimer's disease encode polytopic membrane proteins that are presumed to constitute the catalytic subunit of gamma-secretase, forming a high molecular weight complex with other proteins. During our attempts to identify binding partners of PS2, we cloned CALP (calsenilin-like protein)/KChIP4, a novel member of calsenilin/KChIP protein family that interacts with the C-terminal region of PS. Upon co-expression in cultured cells, CALP was directly bound to and co-localized with PS2 in endoplasmic reticulum. Overexpression of CALP did not affect the metabolism or stability of PS complex, and gamma-cleavage of betaAPP or Notch site 3 cleavage was not altered. However, co-expression of CALP and a voltage-gated potassium channel subunit Kv4.2 reconstituted the features of A-type K(+) currents and CALP directly bound Kv4.2, indicating that CALP functions as KChIPs that are known as components of native Kv4 channel complex. Taken together, CALP/KChIP4 is a novel EF-hand protein interacting with PS as well as with Kv4 that may modulate functions of a subset of membrane proteins in brain.
Morohashi
Yuichi
Y
Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Hatano
Noriyuki
N
Ohya
Susumu
S
Takikawa
Rie
R
Watabiki
Tomonari
T
Takasugi
Nobumasa
N
Imaizumi
Yuji
Y
Tomita
Taisuke
T
Iwatsubo
Takeshi
T
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006801:Humans; D015640:Ion Channel Gating; D051605:Kv Channel-Interacting Proteins; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D053766:Presenilin-2; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D051672:Shal Potassium Channels
C497018:KCND2 protein, human; C496753:KCNIP4 protein, human; C497019:Kcnd2 protein, mouse; C455273:Kcnip4 protein, mouse; D051605:Kv Channel-Interacting Proteins; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D053766:Presenilin-2; D051672:Shal Potassium Channels