# CALCIUM REGULATION SYSTEMS IN SEA URCHIN EGGS

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 1994 · $138,977

## Abstract

Mobilization of intracellular Ca+2 plays an important role in many cellular
processes.  It is generally accepted that inositol trisphosphate is a
second messenger for transducing surface receptor activation to
mobilization of internal Ca+2.  That inositol trisphosphate may not be the
only Ca+2 messenger as suggested by several recent studies.  We have
identified a Ca+2 mobilization system in sea urchin eggs which is totally
independent of the inositol trisphosphate pathway.  This system is
activated by a metabolite of NAD+ we named cyclic ADP-ribose (cADPR).
Evidence we have suggests that cADPR may be an endogenous regulator of the
Ca+2-induced-Ca+2 release mechanism in cells.  Detailed characterization of
the cADPR system should provide useful information toward understanding the
basic mechanisms involved in mobilization of cellular Ca+2.

Research is proposed to elucidate the physiological role of the cADPR
system by, first, determining if cADPR increases the Ca+2 sensitivity of
the Ca+2-induced-Ca+2 release system in intact eggs and homogenates,
second, measuring the endogenous cADPR levels in eggs from fertilization to
cleavage and, third, developing specific inhibitors to block the cADPR
system and assessing the resultant changes in cell functions.  We will
devise methods to purify both the soluble and membrane bound forms of ADP-
ribosyl cyclase, the cADPR synthesizing enzyme, and generate specific
antibodies against them.  Structures of cADPR and the soluble ADP-ribosyl
cyclase from Aplysia ovotestis will be determined by X-ray crystallography.
cADPR will be chemically modified to produce agonists, antagonists and
immunogens of the metabolite.  The degradation enzyme of cADPR will be
characterized.  We will develop methods to radioactively label the
microsomal receptor for cADPR.  Generally applicable procedures for
introducing cADPR into cells will be devised to facilitate the assessment
of how widespread the cADPR system among cells is.  We will characterize
yet another independent Ca+2 release system in egg homogenates that is
activated by a derivative of NADP.

## Key facts

- **NIH application ID:** 2197467
- **Project number:** 5R01HD017484-12
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **SAM.gov UEI:** KABJZBBJ4B54
- **Principal Investigator:** HONCHEUNG LEE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $138,977
- **Award type:** 5
- **Project period:** 1983-04-01 → 1997-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197467

## Citation

> US National Institutes of Health, RePORTER application 2197467, CALCIUM REGULATION SYSTEMS IN SEA URCHIN EGGS (5R01HD017484-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197467. Licensed CC0.

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