Gene encoding for adseverin

Details Gene encoding for adseverin Gene encoding for adseverin

1996-06-28

2000-10-10

Brusca, John S.

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Recombinant dna technique included in method of making a...

4353201, 435325, 536 231, 536 234, C12N 1500, C12N 1563, C12N 1585, C07H 2104

Patent

active

061300608

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

This invention relates to a gene encoding adseverin, which is a Ca.sup.2+ -dependent actin filament-severing protein and has a function of regulating exocytosis, a recombinant vector containing this gene, a recombinant transformed by this vector, a process for producing adseverin by using the above-mentioned gene and a recombinant adseverin protein obtained by this process. The present invention also relates to an oligonucleotide hybridizable specifically with a base sequence encoding the adseverin protein, a method for regulating the formation of adseverin which comprises administering an oligonucleotide hybridizable specifically with a base sequence encoding the adseverin protein to an animal, and an antibody capable of recognizing the adseverin protein.


BACKGROUND ART

In many secretory cells in the resting state, secretion products such as neurotransmitters and hormones are stored in the form of granules or vesicles. When the cells receive adequate signals, these substances are released from the cells by exocytosis. In the process of exocytosis, the granules and vesicles migrate toward plasma membrane. Then they come into contact with the plasma membrane followed by fusion therewith, thus opening the membrane.
This exocytosis is tightly controlled by the concentration of intracellular free calcium [Ca.sup.2+ ].sub.i (Knight et al., Ann. N.Y. Acad. Sci. 493: 504-523, 1987). Namely, it is considered that in resting cells where [Ca.sup.2+ ].sub.i is low, exocytosis is blocked at several steps depending on [Ca.sup.2+ ].sub.i (Burgoyne, Biochem. Biophys. Acta 779: 201-216, 1984). A number of secretory cells including chromaffin cells which are adrenal medulla secretory cells have a microfilament network composed of actin filaments under the plasma membrane which is supposed to serve as a barrier against the migration of granules and vesicles toward the plasma membrane (Cheek et al., FEBS Lett. 207: 110-114, 1986; Lelkes et al., FBES Lett. 208: 357-363, 1986). Prior to the release of the secretion products by exocytosis, this network is disassembled due to the increase in [Ca.sup.2+ ].sub.i by Ca.sup.2+ -dependent mechanisms (Vitale et al., J. Cell Biol. 113: 1057-1067, 1991).
Actin is a globular protein with a molecular weight of 42 kD which is commonly distributed in eukaryocytes. It is a cytoskeleton protein closely relating to the contraction of muscle cells, etc. Actin monomers are polymerized to form filaments. Under the physiological ionic strength, actin undergoes polymerization in vitro at a ratio of about 100% so as to give filaments. In actual cells, however, various actin-regulating proteins contribute to the reversible conversion of filaments (gel) and monomers (sol) and changes occur depending on extracellular stimuli.
In bovine chromaffin cells, gelsolin, which seemingly relates directly to this process, was identified (Yin et al., Nature 281: 583-586, 1979). Gelsolin shows a Ca.sup.2+ -dependent actin filament severing activity in vitro and exerts barbed end capping and nucleating activities on actin filaments.
Recently, adseverin (a protein of 74 kDa), which is similar to gelsolin in activity but different from it, was isolated from bovine adrenal medulla by Prof. Nonomura et al., Department of Pharmacology, Faculty of Medicine, University of Tokyo (Maekawa et al., J. Biol. Chem. 265: 10940-10942).
Gelsolin is relatively widely distributed in various tissues and blood plasma (Stossel et al., Annu. Rev. Cell Biol. 1: 353-402, 1985), while the distribution of adseverin is restricted mainly to the tissues with secretory functions (Sakurai et al., Neuroscience 38: 743-756, 1990). This difference in tissue distribution of these proteins suggests that adseverin more closely relates to the secretory process (i.e., control of the release of neurotransmitters, endocrine substances or physiologically active substances) than gelsolin does. Accordingly, it is highly interesting to reveal the structure and function of adseverin to thereby clarify the role and regulatory mechanisms of a

REFERENCES:
Berendsen, A glimpse of the holy grail, Science, vol. 282, pp. 642-643, Oct. 1998.
Database EMBL, Entry MM04354, Accession No. U04354, Dec. 17, 1993.
A. Rodriquez et al., The EMBO Journal, vol. 9, No. 1, pp. 43-52 (1990).
L. Tchakarov et al., FEBS Letters, vol. 268, No. 1, pp. 209-212 (1990).
M. G. Marcu et al., Molecular and Cellular Biochemistry, vol. 141, No. 2, pp. 153-165 (1994).
P. A. Janmey et al., Blood, vol. 80, No. 4, pp. 928-936 (1992).

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