Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4

Yuichi Morohashi, Noriyuki Hatano, Susumu Ohya, Rie Takikawa, Tomonari Watabiki, Nobumasa Takasugi, Yuji Imaizumi, Taisuke Tomita, Takeshi Iwatsubo

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Presenilin (PS) genes linked to early-onset familial Alzheimer's disease encode polytopic membrane proteins that are presumed to constitute the catalytic subunit of γ-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 γ-cleavage of βAPP 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.

Original languageEnglish
Pages (from-to)14965-14975
Number of pages11
JournalJournal of Biological Chemistry
Volume277
Issue number17
DOIs
Publication statusPublished - Apr 26 2002
Externally publishedYes

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Kv Channel-Interacting Proteins
Presenilin-2
EF Hand Motifs
Voltage-Gated Potassium Channels
Cloning
Molecular Cloning
Presenilins
Proteins
Alzheimer Disease
Membrane Proteins
Amyloid Precursor Protein Secretases
Set theory
Metabolism
Endoplasmic Reticulum
Cultured Cells
Brain
Catalytic Domain

ASJC Scopus subject areas

  • Biochemistry

Cite this

Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4. / Morohashi, Yuichi; Hatano, Noriyuki; Ohya, Susumu; Takikawa, Rie; Watabiki, Tomonari; Takasugi, Nobumasa; Imaizumi, Yuji; Tomita, Taisuke; Iwatsubo, Takeshi.

In: Journal of Biological Chemistry, Vol. 277, No. 17, 26.04.2002, p. 14965-14975.

Research output: Contribution to journalArticle

Morohashi, Yuichi ; Hatano, Noriyuki ; Ohya, Susumu ; Takikawa, Rie ; Watabiki, Tomonari ; Takasugi, Nobumasa ; Imaizumi, Yuji ; Tomita, Taisuke ; Iwatsubo, Takeshi. / Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 17. pp. 14965-14975.
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