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Hippocalcin, new Ca2+ sensor of a ROS-GC subfamily member, ONE-GC, membrane guanylate cyclase transduction system

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Abstract

Hippocalcin is a member of the neuronal Ca2+ sensor protein family. Among its many biochemical functions, its established physiological function is that via neuronal apoptosis inhibitory protein it protects the neurons from Ca2+-induced cell death. The precise biochemical mechanism/s, through which hippocalcin functions, is not clear. In the present study, a new mechanism by which it functions is defined. The bovine form of hippocalcin (BovHpca) native to the hippocampus has been purified, sequenced, cloned, and studied. The findings show that there is the evolutionary conservation of its structure. It is a Ca2+-sensor of a variant form of the ROS-GC subfamily of membrane guanylate cyclases, ONE-GC. It senses physiological increments of Ca2+ with a K1/2 of 0.5 µM and stimulates ONE-GC or ONE-GC-like membrane guanylate cyclase. The Hpca-modulated ONE-GC-like transduction system exists in the hippocampal neurons. And hippocalcin-modulated ONE-GC transduction system exists in the olfactory receptor neuroepithelium. The Hpca-gene knock out studies demonstrate that the portion of this is about 30% of the total membrane guanylate cyclase transduction system. The findings establish Hpca as a new Ca2+ sensor modulator of the ROS-GC membrane guanylate cyclase transduction subfamily. They support the concept on universality of the presence and operation of the ROS-GC transduction system in the sensory and sensory-linked neurons. They validate that the ROS-GC transduction system exists in multiple forms. And they provide an additional mechanism by which ROS-GC subfamily acts as a transducer of the Ca2+ signals originating in the neurons.

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Abbreviations

DTT:

1,4-Dithiothreitol

EDTA:

Ethylenediaminetetraacetic acid

EGTA:

Ethylene glycol bis (2-aminoethyl ether)-N,N,N′,N′-tetraacetic acid

GCAP:

Guanylate cyclase activating protein

HEPES:

1-Piperazineethane sulfonic acid, 4-(2-hydroxyethyl)-monosodium salt

ONE-GC:

Olfactory neuroepithelial membrane guanylate cyclase

PMSF:

Phenylmethylsulphonylfluoride

ROS-GC:

Rod outer segment membrane guanylate cyclase

SDS-PAGE:

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis

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Acknowledgment

This research was supported by USPHS awards DC 005349 (RKS) and HL084584 (TD) and a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sport and Technology of Japan (KT).

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  1. Anuradha Krishnan

    Present address: Department of Cell Biology, UMDNJ-SOM, Stratford, NJ, USA

Authors and Affiliations

  1. The Unit of Regulatory and Molecular Biology, Division of Biochemistry and Molecular Biology, Salus University, Elkins Park, PA, 19027, USA

    Teresa Duda, Alexandre Pertzev & Rameshwar K. Sharma

  2. Department of Physiology, Toho University School of Medicine, 5-12-16 Ohmori-nishi, Ohta-ku, Tokyo, 143-8540, Japan

    Masaaki Kobayashi & Ken Takamatsu

Authors
  1. Anuradha Krishnan
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  2. Teresa Duda
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  3. Alexandre Pertzev
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  4. Masaaki Kobayashi
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  6. Rameshwar K. Sharma
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Correspondence to Rameshwar K. Sharma.

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Anuradha Krishnan and Teresa Duda have contributed equally to this work.

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Krishnan, A., Duda, T., Pertzev, A. et al. Hippocalcin, new Ca2+ sensor of a ROS-GC subfamily member, ONE-GC, membrane guanylate cyclase transduction system. Mol Cell Biochem 325, 1–14 (2009). https://doi.org/10.1007/s11010-008-0015-z

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