Chromogranin A
Geoffrey N. Hendy
Sarah Bevan
Marie-Geneviève Mattei
Andrew J. Mouland
Calcium Research Laboratory and Departments of
Medicine and Physiology, McGill University and
Royal Victoria Hospital, Montreal, Quebec;
Hôpital d'Enfants de la Timone, Centre de
Génétique Medicale, Marseille, France
(Original manuscript submitted 10/3/94; received in revised form
1/6/94; accepted 7/6/94)
Abstract
Chromogranin A (CgA) is the major member of the granin family of
acidic secretory glycoproteins that are expressed in all endocrine and
neuroendocrine cells. Granins have been proposed to play multiple
roles in the secretory process. Intracellularly, granins play a role in
targeting peptide hormones and neurotransmitters to granules of the
regulated pathway by virtue of their ability to aggregate in the low-pH,
high-calcium environment of the trans-Golgi network.
Extracellularly, peptides formed as a result of proteolytic processing
of granins regulate hormone secretion. Some conserved features of
the mature CgA protein are polyglutamic acids, calcium-binding sites,
and several pairs of basic amino acids. The first 2 features are
important for its intracellular functions, and the latter characteristic
suggested that peptides could be released from the molecule by
precursor processing enzymes. Several biologically active peptides
encoded within the CgA molecule, such as vasostatin, beta-granin,
chromostatin, pancreastatin, and parastatin act predominantly to
inhibit hormone and neurotransmitter release in an autocrine or
paracrine fashion. The biosynthesis of CgA is regulated by many
different factors, including steroid hormones and agents that act
through a variety of signalling pathways. CgA biosynthesis and that
of the resident hormone or neurotransmitter can be regulated
differentially. The widespread distribution of CgA has made the
measurement of circulating immunoreactive CgA a valuable tool in the
diagnosis of neuroendocrine neoplasia, and CgA
immunohistochemistry can help to identify the neuroendocrine nature
of tumours. Recent molecular biology studies are identifying those
elements in the CgA gene promoter responsible for its specific
neuroendocrine cell expression.
Clin Invest Med 1995; 18 (1): 47-65
Table of contents: CIM vol. 18, no. 1
Copyright 1996 Canadian Medical Association