ISSN 10623604, Russian Journal of Developmental Biology, 2010, Vol. 41, No. 5, pp. 318–325. © Pleiades Publishing, Inc., 2010.
Original Russian Text © N.N. Nemova, L.A. Lysenko, N.P. Kantserova, 2010, published in Ontogenez, 2010, Vol. 41, No. 5, pp. 381–389.
Proteolysis is one of the universal processes of nature;
at present, it is considered a basic mechanism of bio
chemical control (Antonov, 1983; Kirschner, 2000).
Modern techniques of protein chemistry, molecular biol
ogy, and bioinformatics allow for identifying more
extremely various classes and families of proteases using
different mechanisms of catalysis for substrate hydrolysis
and which would conform to a wide range of formation
conditions in several organisms. Bioinformatic analysis of
the human genome showed that proteases and their inac
tive homologous were coded by 1.7% of structural genes;
therefore, they formed the most numerous group of
enzymes including 570 specimens that exceeded the
kinase pool (456 enzymes) and conceded only to proteins
of family of transcription factors (Rawlings et al., 2004).
Cellular proteolytic apparatus is highly selective and is
strictly regulated, whereas extra disrupture of vital pro
teins or delayed degradation of shortterm regulatory pro
teins can change cellular functions significantly.
CALPAINS AS A COMPONENT
OF PROTEOLYTIC APPARATUS OF CELL
Intracellular degradation of proteins in eucaryotes
and, probably, in many prokaryotes is a result of the coop
eration of calpains, lysosomal catepsins, and proteasomes
(Goll et al., 2003); furthermore, calpains (EC 22.214.171.124)
are responsible for initiation of the process (Cottin et al.,
1994). Calpains are constitutive enzymes but, on the basis
of the results of a number of studies (Cottin et al., 1994),
it is impossible to consider them as “household” proteins,
because transcription of their genes is under regulation.
However, physiologic functions of calpains are still not
clear; it is suggested that they are characterized by regula
tory and signal functions more than catabolic typical for
lysosomal proteases and proteasomes (Goll et al., 2003).
Calpains participate in general calciumdependent cellu
lar processes—signal transduction, cell cycle, prolifera
tion, differentiation, migration, apoptosis, membrane
fusion, formation of muscle fibers, and others (Sorimachi
et al., 1997; Goll et al., 2003); change of their activity was
described at some metabolic disorders and degenerative
disease (Tidball and Spencer, 2000; Suzuki et al., 2004).
Immunological studies showed that calpains are
located only in cells (Goll et al., 2003). The main pool of
calpains is dissolved in cytosol; furthermore, using charge
loops (Strobl et al., 2000) calpains are able to associate
with cell membrane and subcellular organelles, such as
myofibrils of skeletal muscles, cytoskeleton elements of
nonmuscular cells, membranes of endoplasmic reticulum
(EPR), and Goldgi apparatus (GA), and to enter lumens
of these organelles (Hood et al., 2004). Calpastatin—
endogenous inhibitor of calpains—is found on the sur
face of EPR and GA as peripheric protein (Hood et al.,
2004). When tissues are damaged, an elimination of active
calpain in blood channels and intercellular matrix is pro
vided by plasma inhibitors—
other proteins (Crawford, 1990).
Calpains occur in most organisms: from bacteria to
human, except archaebacteria and viruses. Analysis of
complete or partially deduced genomes of organisms
(Croall and Ersfeld, 2007) showed that only a few of them
have no genes of calpains; a single gene of calpain was
found in bacteria, most protists, fungi, and plants,
whereas in most vertebrates and actually in a number of
parasitic kinetoplastides and infusoria there are a lot of
related genes of calpains. Most enzymes encoded by these
genes are still not found; therefore, not so much is known
about their properties (Bondareva et al., 2006; Bondareva
and Nemova, 2008; Goll et al., 2003).
Proteases of the Calpain Family: Structure and Functions
N. N. Nemova, L. A. Lysenko, and N. P. Kantserova
Institute of Biology, Karelian Research Centre, Russian Academy of Sciences,
ul. Pushkinskaya 11, Petrozavodsk, 185910 Russia
Received February 16, 2010; in final form, February 19, 2010
—Results of studies presented in recent papers and personal data related to investigation of struc
ture, classification, phylogeny of calciumdependent peptidases or calpains have been analyzed. The most
extensively studied functions of calpains in cell activity have been examined. Some not yet resolved questions
concerned with the biological role of a great number of proteins of the calpain family have been defined.
: proteolysis, calpains, regulation, functions
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