INTRODUCTION
Satellite cells, also called adult myoblasts or muscle precursor
cells, were first described by Mauro (1961). These mononucleate
cells are located between the basement membrane and the plasma
membrane of the muscle fiber. A large body of literature has
indicated that satellite cells provide myofiber nuclei in the
growing muscles. These cells are also activated in injured
muscles, where their progeny differentiate and fuse to reconstitute
the wounded muscle fibers (for review see Hartley and Yablonka-
Reuveni, 1992). In contrast to some commonly used myogenic
cell lines such as C2.7, culture of primary satellite cells offers the
opportunity to observe complete myogenic differentiation very
similar to that occuring in vivo. Myoblasts proliferate, become
postmitotic, and differentiate into large multinucleate myotubes
which spontaneously contract about 11-12 days after plating
(Campion, 1983; Le Moigne et al., 1990).
The exit from cell cycling and the differentiation process most
likely involve significant alterations of the intracellular protein
pool mediated by reprogramming and cytoplasmic site-specific
targeting of mRNA expression, and by proteolytic activity.
Furthermore, myogenesis involves profound reorganization of the
cell structure. Thus, during the fusion of the individual myogenic
precursor cells into the syncitial myotubes, the cytoskeletal
framework is dramatically modified in relation to the creation of
a functional sarcomeric organization.
During the course of myogenic differentiation, numerous
factors may exert specific control at different key steps. Among
the factors acting in myoblast maturation, prosomes appear to
be important in view of their multiple biological roles. These
particles constitute the proteolytic core of the 26S proteasomes
(therefore, also called ‘multicatalytic proteinase’ (MCP) or
‘20S proteasomes’) and also have RNase activities. The 26S
proteasomes (‘MCP-complex’ or ‘MCP-C’) were originally
found as components of the untranslated mRNA complexes in
the cytoplasm and, more recently, as components of pre-
mRNPs and the nuclear matrix. They may thus be considered
as cellular factors playing an important role in the homeostasis
of cellular proteins by protein biosynthesis and breakdown (for
review see Coux et al., 1996; Scherrer and Bey, 1994).
The prosome particles, first found associated with untranslated
mRNPs, may be considered trans-acting factors acting at
transcriptional and post-transcriptional levels of gene expression.
Prosomes were found on interphase chromosomes, the nuclear
matrix and pre-mRNP (Pal et al., 1988; E. Pilotti et al.,
unpublished), and cytoplasmic mRNP but not in polyribosomes
989 Journal of Cell Science 112, 989-1001 (1999)
Printed in Great Britain © The Company of Biologists Limited 1999
JCS9866
Myogenesis proceeds by fusion of proliferating myoblasts
into myotubes under the control of various transcription
factors. In adult skeletal muscle, myogenic stem cells are
represented by the satellite cells which can be cultured and
differentiate in vitro. This system was used to investigate the
subcellular distribution of a particular type of prosomes at
different steps of the myogenic process. Prosomes constitute
the MCP core of the 26S proteasomes but were first
observed as subcomplexes of the untranslated mRNPs;
recently, their RNase activity was discovered. A monoclonal
antibody raised against the p27K subunit showed that the
p27K subunit-specific prosomes move transiently into the
nucleus prior to the onset of myoblast fusion into myotubes;
this represents possibly one of the first signs of myoblast
switching into the differentiation pathway. Prior to fusion,
the prosomes containing the p27K subunit return to the
cytoplasm, where they align with the gradually formed
lengthwise-running desmin-type intermediate filaments and
the microfilaments, co-localizing finally with the actin
bundles. The prosomes progressively form discontinuous
punctate structures which eventually develop a pseudo-
sarcomeric banding pattern. In myotubes just formed in
vitro, the formation of this pattern seems to preceed that
produced by the muscle-specific sarcomeric α-actin.
Interestingly, this pattern of prosomes of myotubes in
terminal in vitro differentiation was very similar to that of
prosomes observed in vivo in foetal and adult muscle. These
observations are discussed in relation to molecular
myogenesis and prosome/proteasome function.
Key words: Prosome, Proteasome, Cytoskeleton, Satellite cell,
Myogenesis, Sarcomere
SUMMARY
Dynamic distribution and formation of a para-sarcomeric banding pattern of
prosomes during myogenic differentiation of satellite cells in vitro
J. Foucrier
1,
*, M. C. Grand
1
, F. De Conto
2,3
, Y. Bassaglia
1
, G. Géraud
2
, K. Scherrer
2
and I. Martelly
1
1
CRRET, UPRESA-CNRS 7053, Université Paris 12, Av. du Général de Gaulle, 94010 Créteil Cedex, France
2
Institut Jacques Monod, Université Paris 7, 2, place Jussieu, 75251 Paris Cedex 05, France
3
Istituto di Microbiologia, Università degli Studi, Viale A. Gramsci 14, 43100 Parma, Italy
*Author for correspondence
Accepted 13 January; published on WWW 10 March 1999