Histidine-rich Ca-binding protein interacts with sarcoplasmic reticulum Ca-ATPase

Demetrios A. Arvanitis, Elizabeth Vafiadaki, Guo Chang Fan, Bryan A. Mitton, Kimberly N. Gregory, Federica Del Monte, Aikaterini Kontrogianni-Konstantopoulos, Despina Sanoudou, Evangelia G. Kranias

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Depressed cardiac Ca cycling by the sarcoplasmic reticulum (SR) has been associated with attenuated contractility, which can progress to heart failure. The histidine-rich Ca-binding protein (HRC) is an SR component that binds to triadin and may affect Ca release through the ryanodine receptor. HRC overexpression in transgenic mouse hearts was associated with decreased rates of SR Ca uptake and delayed relaxation, which progressed to hypertrophy with aging. The present study shows that HRC may mediate part of its regulatory effects by binding directly to sarco(endo)plasmic reticulum Ca-ATPase type 2 (SERCA2) in cardiac muscle, which is confirmed by coimmunostaining observed under confocal microscopy. This interaction involves the histidine- and glutamic acid-rich domain of HRC (320-460 aa) and the part of the NH2- terminal cation transporter domain of SERCA2 (74-90 aa) that projects into the SR lumen. The SERCA2-binding domain is upstream from the triadin-binding region in human HRC (609-699 aa). Specific binding between HRC and SERCA was verified by coimmunoprecipitation and pull-down assays using human and mouse cardiac homogenates and by blot overlays using glutathione S-transferase and maltose-binding protein recombinant proteins. Importantly, increases in Ca concentration were associated with a significant reduction of HRC binding to SERCA2, whereas they had opposite effects on the HRC-triadin interaction in cardiac homogenates. Collectively, our data suggest that HRC may play a key role in the regulation of SR Ca cycling through its direct interactions with SERCA2 and triadin, mediating a fine cross talk between SR Ca uptake and release in the heart.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number3
DOIs
Publication statusPublished - 1 Sep 2007
Externally publishedYes

Fingerprint

Sarcoplasmic Reticulum
Histidine
Adenosine Triphosphatases
Carrier Proteins
Reticulum
Maltose-Binding Proteins
Ryanodine Receptor Calcium Release Channel
Glutathione Transferase
Recombinant Proteins
Protein Binding
Confocal Microscopy
Hypertrophy
Transgenic Mice
Cations
Glutamic Acid
Myocardium
Heart Failure
triadin

Keywords

  • Calcium cycling
  • Triadin

ASJC Scopus subject areas

  • Physiology

Cite this

Arvanitis, D. A., Vafiadaki, E., Fan, G. C., Mitton, B. A., Gregory, K. N., Del Monte, F., ... Kranias, E. G. (2007). Histidine-rich Ca-binding protein interacts with sarcoplasmic reticulum Ca-ATPase. American Journal of Physiology - Heart and Circulatory Physiology, 293(3). https://doi.org/10.1152/ajpheart.00278.2007

Histidine-rich Ca-binding protein interacts with sarcoplasmic reticulum Ca-ATPase. / Arvanitis, Demetrios A.; Vafiadaki, Elizabeth; Fan, Guo Chang; Mitton, Bryan A.; Gregory, Kimberly N.; Del Monte, Federica; Kontrogianni-Konstantopoulos, Aikaterini; Sanoudou, Despina; Kranias, Evangelia G.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 293, No. 3, 01.09.2007.

Research output: Contribution to journalArticle

Arvanitis, DA, Vafiadaki, E, Fan, GC, Mitton, BA, Gregory, KN, Del Monte, F, Kontrogianni-Konstantopoulos, A, Sanoudou, D & Kranias, EG 2007, 'Histidine-rich Ca-binding protein interacts with sarcoplasmic reticulum Ca-ATPase', American Journal of Physiology - Heart and Circulatory Physiology, vol. 293, no. 3. https://doi.org/10.1152/ajpheart.00278.2007
Arvanitis, Demetrios A. ; Vafiadaki, Elizabeth ; Fan, Guo Chang ; Mitton, Bryan A. ; Gregory, Kimberly N. ; Del Monte, Federica ; Kontrogianni-Konstantopoulos, Aikaterini ; Sanoudou, Despina ; Kranias, Evangelia G. / Histidine-rich Ca-binding protein interacts with sarcoplasmic reticulum Ca-ATPase. In: American Journal of Physiology - Heart and Circulatory Physiology. 2007 ; Vol. 293, No. 3.
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