Skeletal muscle effects of electrostimulation after COPD exacerbation: a pilot study.

Muscle dysfunction is a major problem in chronic obstructive pulmonary disease (COPD), particularly after exacerbations. We thus asked whether neuromuscular electrostimulation (NMES) might be directly useful following an acute exacerbation and if such a therapy decreases muscular oxidative stress and/or alters muscle fibre distribution. A pilot randomised controlled study of NMES lasting 6 weeks was carried out in 15 in-patients (n=9 NMES; n=6 sham) following a COPD exacerbation. Stimulation was delivered to the quadriceps and hamstring muscles (35 Hz). Primary outcomes were quadriceps force and muscle oxidative stress. At the end of the study, quadriceps force improvement was statistically different between groups (p=0.02), with a significant increase only in the NMES group (median (interquartile range) 10 (4.7-11.5) kg; p=0.01). Changes in the 6-min walking distance were statistically different between groups (p=0.008), with a significant increase in the NMES group (165 (125-203) m; p=0.003). NMES did not lead to higher muscle oxidative stress, as indicated by the decrease in total protein carbonylation (p=0.02) and myosin heavy chain carbonylation (p=0.01) levels. Finally, we observed a significant increase in type I fibre proportion in the NMES group. Our study shows that following COPD exacerbation, NMES is effective in counteracting muscle dysfunction and decreases muscle oxidative stress.

In vitro mouse model in Duchenne muscular dystrophy diagnosis using 50-MHz ultrasound waves.

Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin, the protein that plays a key mechanical role in maintaining muscle membrane integrity. One of the major consequences of dystrophin deficiency is the degeneration of muscle fibres, with a progressive loss in muscle strength. The objective of this research was to find an ultrasonic parameter sensitive to DMD, which could give relevant information related to microstructure if compared to traditional investigations such as morphometrical analysis. This "in vitro" study focused on the Mdx mouse model and investigated the potential differences between wild-type and dystrophin-deficient mice diaphragms. Using a 50MHz ultrasonic sensor built in our group, we recorded an increase in ultrasonic wave attenuation in the dystrophin-deficient samples in comparison with normal muscles. A correlation between attenuation, mouse age and the percentage of non-muscular proportion in muscle was observed. As Mdx mouse is the best animal model for DMD and reproduces the degenerative pattern observed in human DMD muscles, this approach could be a powerful tool for in vitro DMD investigation and, more generally, for the characterisation of muscle properties.

Effect of beta-dystroglycan processing on utrophin/Dp116 anchorage in normal and mdx mouse Schwann cell membrane.

In the peripheral nervous system, utrophin and the short dystrophin isoform (Dp116) are co-localized at the outermost layer of the myelin sheath of nerve fibers; together with the dystroglycan complex. Dp116 is associated with multiple glycoproteins, i.e. sarcoglycans, and alpha- and beta-dystroglycan, which anchor the cytoplasmic protein subcomplex to the extracellular basal lamina. In peripheral nerve, matrix metalloproteinase activity disrupts the dystroglycan complex by cleaving the extracellular domain of beta-dystroglycan. Metalloproteinase creates a 30 kDa fragment of beta-dystroglycan, leading to a disruption of the link between the extracellular matrix and the cell membrane. Here we asked if the processing of the beta-dystroglycan could influence the anchorage of Dp116 and/or utrophin in normal and mdx Schwann cell membrane. We showed that metalloproteinase-9 was more activated in mdx nerve than in wild-type ones. This activation leads to an accumulation of the 30 kDa beta-dystroglycan isoform and has an impact on the anchorage of Dp116 and utrophin isoforms in mdx Schwann cells membrane. Our results showed that Dp116 had greater affinity to the full length form of beta-dystroglycan than the 30 kDa form. Moreover, we showed for the first time that the short isoform of utrophin (Up71) was over-expressed in mdx Schwann cells compared with wild-type. In addition, this utrophin isoform (Up71) seems to have greater affinity to the 30 kDa beta-dystroglycan which could explain the increased stabilization of this 30 kDa form at the membrane compartment. Our results highlight the potential participation of the short utrophin isoform and the cleaved form of beta-dystroglycan in mdx Schwann cell membrane architecture. We proposed that these two proteins could be implicated in Schwann cell proliferation in response to a microenvironment stress such as mediated by accumulating macrophages in mdx mouse muscle inflammation sites.

Monocarboxylate transporters, blood lactate removal after supramaximal exercise, and fatigue indexes in humans.

The present study investigated whether muscular monocarboxylate transporter (MCT) 1 and 4 contents are related to the blood lactate removal after supramaximal exercise, fatigue indexes measured during different supramaximal exercises, and muscle oxidative parameters in 15 humans with different training status. Lactate recovery curves were obtained after a 1-min all-out exercise. A biexponential time function was then used to determine the velocity constant of the slow phase (gamma(2)), which denoted the blood lactate removal ability. Fatigue indexes were calculated during 1-min all-out (FI(AO)) and repeated 10-s (FI(Sprint)) cycling sprints. Biopsies were taken from the vastus lateralis muscle. MCT1 and MCT4 contents were quantified by Western blots, and maximal muscle oxidative capacity (V(max)) was evaluated with pyruvate + malate and glutamate + malate as substrates. The results showed that the blood lactate removal ability (i.e., gamma(2)) after a 1-min all-out test was significantly related to MCT1 content (r = 0.70, P < 0.01) but not to MCT4 (r = 0.50, P > 0.05). However, greater MCT1 and MCT4 contents were negatively related with a reduction of blood lactate concentration at the end of 1-min all-out exercise (r = -0.56, and r = -0.61, P < 0.05, respectively). Among skeletal muscle oxidative indexes, we only found a relationship between MCT1 and glutamate + malate V(max) (r = 0.63, P < 0.05). Furthermore, MCT1 content, but not MCT4, was inversely related to FI(AO) (r = -0.54, P < 0.05) and FI(Sprint) (r = -0.58, P < 0.05). We concluded that skeletal muscle MCT1 expression was associated with the velocity constant of net blood lactate removal after a 1-min all-out test and with the fatigue indexes. It is proposed that MCT1 expression may be important for blood lactate removal after supramaximal exercise based on the existence of lactate shuttles and, in turn, in favor of a better tolerance to muscle fatigue.

Formation of multiple complexes between beta-dystroglycan and dystrophin family products.

Beta-dystroglycan is expressed in a wide variety of tissues and has generally been reported with an Mr of 43 kDa, sometimes accompanied with a 31 kDa protein assumed to be a truncated product. This molecule was recently identified as the anomalous beta-dystroglycan expressed in various carcinoma cell lines. We produced and characterized a G5 polyclonal antibody specific to beta-dystroglycan that is directed against the C-terminal portion of the molecule. We provide evidence that beta-dystroglycan may vary in size and properties by studying different Xenopus tissues. Besides normal beta-dystroglycan with an Mr of 43 kDa in smooth and cardiac muscle and sciatic nerve extracts, we found it in skeletal muscle and brain proteins with an Mr of 38 and 65 kDa, respectively. Glycosylation properties and proteolytic susceptibilities of these different beta-dystroglycans are analysed and compared in this work. Crosslinking experiments with various beta-dystroglycan preparations obtained from skeletal and cardiac muscles and brain gave rise to specific new covalent products with Mr of 125 kDa (doublet band), or 120 and 130 kDa, or 140 and 240 kDa, respectively. We provide evidence, using various similar beta-dystroglycan preparations, that the immunoprecipitation procedure with G5 specific polyclonal antibody allows consistent pelleting of various dystrophin-family isoforms. Skeletal muscles from Xenopus reveals the presence of two distinct beta-dystroglycan complexes, one with dystrophin and another one which involves alpha-dystrobrevin. Cardiac muscle and brain from Xenopus are shown to contain three beta-dystroglycan complexes related to various dystrophin-family isoforms. Dystrophin or alpha-dystrobrevin or Dp71 were found in cardiac muscle and dystrophin or Dp180 or Up71 in brain. This variability in the relationship between beta-dystroglycan and dystrophin-family isoforms suggests that each protein--currently known as dystrophin associated protein--could not be present in each of these complexes.

Dystrophin and dystrophin-associated protein in muscles and nerves from monkey.

Since all organs (i.e. skeletal, cardiac, smooth muscles and sciatic nerve) are never only taken from a single patient, all these tissues were obtained from one cynomolgus monkey, a model closely resembling humans. This work describes an up-to-date reinvestigation of the dystrophin-glycoprotein complex and related molecules in various monkey tissues such those cited above. We used monoclonal and polyclonal antibodies produced in our laboratory, which are directed against dystrophin, utrophin, short-dystrophin products, alpha-dystrobrevin, beta-dystroglycan, alpha-syntrophin, alpha-, beta-, gamma-, delta-, epsilon-sarcoglycan, and sarcospan. For each molecule, we determined their molecular weight and tissue localization. Regardless of the tissue analyzed, at least one dystrophin or utrophin as full-length molecule and one short-dystrophin product or dystrobrevin as proteins belonging to the dystrophin superfamily were found. Beta-dystroglycan, beta and delta sarcoglycans were always detected, while other sarcoglycans varied from all to only three components. Epsilon sarcoglycan appears to be specific to smooth muscle, which is devoid of alpha sarcoglycan. Sarcospan is only absent from sciatic nerve structures. Among the different muscles investigated in this study, short dystrophin products are only present in cardiac muscle. All of these findings are summarized in one table, which highlight in one single animal the variability of the dystrophin-glycoprotein complex components in relation with the organ studied. This statement is important because any attempt to estimate protein restoration needs in each study the knowledge of the expected components that should be considered normal.

Dystrophin-associated proteins in obliquely striated muscle of the leech Pontobdella muricata (Annelida, Hirudinea).

The distribution of dystrophin-associated proteins (beta-dystroglycan, alpha-, beta-, gamma- and delta-sarcoglycan, alpha-syntrophin and sarcospan) were studied in obliquely striated muscle of the leech Pontobdella muricata. Western blot analysis and immunohistochemical electron microscopy, using various polyclonal antibodies, were employed. Western blot analysis of all of these antibodies showed a single band, with approximately the same molecular weights as similar proteins detected in vertebrate muscles. The immunoelectron microscopy study confirmed specific immunogold labelling in the membrane of muscle cells. Since all dystrophin complex components have similar molecular weights and the same localisation in leech as in vertebrate skeletal muscle, we assume that these proteins have similar properties in leech and vertebrate muscle. The presence of these molecules in annelid muscles, together with a short version of dystrophin (previously described as IDLp-140) is of particular interest since phylogenetic and functional studies on this material could help to shed new light on the role and function of this complex in the muscle membrane.

Comparative evolution of muscular dystrophy in diaphragm, gastrocnemius and masseter muscles from old male mdx mice.

X chromosome-linked muscular dystrophic mdx mouse lacks the sarcolemmal protein dystrophin and represents a genetic homologue of human Duchenne muscular dystrophy (DMD). The present study analysed some aspects of pathological processes such as fibrosis, frequency of centralized nuclei, presence of degenerative or regenerative fibres, expression of utrophin and associated protein complexes, and myosin heavy chain isoforms in three muscles [diaphragm (DIA), gastrocnemius (GTC) and masseter (MAS)] from old male mdx mice. All parameters investigated comparatively in these pathological muscles provided evidence that the MAS mdx muscle presents a slight deterioration pattern in comparison to that of DIA and GTC muscles. Utrophin and associated proteins are present in many cell clusters with continuous membrane labelling in MAS muscle. Respective proportions of myosin heavy chain isoforms, measured by electrophoresis/densitometry, showed only slight change in GTC muscle, significant evolution in DIA muscle but drastic isoform conversions in MAS muscle. These results highlighted the difference in deterioration susceptibility of various muscles to muscular dystrophy. The reason why this occurs in MAS muscles is still obscure and discussed in terms of the comparative developmental origins of these muscles.

Variations in dystrophin complex in red and white caudal muscles from Torpedo marmorata.

We present an up-to-date study on the nature, at the protein level, of various members of the dystrophin complex at the muscle cell membrane by comparing red and white caudal muscles from Torpedo marmorata. Our investigations involved immunodetection approaches and Western blotting analysis. We determined the presence or absence of different molecules belonging to the dystrophin family complex by analyzing their localization and molecular weight. Specific antibodies directed against dystrophin, i.e., DRP2 alpha-dystrobrevin, beta-dystroglycan, alpha-syntrophin, alpha-, beta-, gamma-, and delta-sarcoglycan, and sarcospan, were used. The immunofluorescence study (confocal microscopy) showed differences in positive immunoreactions at the sarcolemmal membrane in these slow-type and fast-type skeletal muscle fibers. Protein extracts from T. marmorata red and white muscles were analyzed by Western blotting and confirmed the presence of dystrophin and associated proteins at the expected molecular weights. Differences were confirmed by comparative immunoprecipitation analysis of enriched membrane preparations with anti-beta-dystroglycan polyclonal antibody. These experiments revealed clear complex or non-complex formation between members of the dystrophin system, depending on the muscle type analyzed. Differences in the potential function of these various dystrophin complexes in fast or slow muscle fibers are discussed in relation to previous data obtained in corresponding mammalian tissues. (J Histochem Cytochem 49:857-865, 2001)

Presence of invertebrate dystrophin-like products in obliquely striated muscle of the leech, Pontobdella muricata (Annelida, Hirudinea).

Dystrophin is a 427-kDa cytoskeletal protein, which occurs in scant amounts in vertebrate muscle and nerve cells. No previous references to dystrophin or associated proteins in invertebrates at the protein level have been found, while two recent studies investigated the presence of genes encoding proteins homologous to dystrophin in sea urchin and other invertebrates such as Drosophila melanogaster. In this study, the possible presence and distribution of dystrophin-like proteins were studied in different invertebrate muscle cell types and species through Western blot analysis and light and electron microscope immunohistochemistry using a panel of antibodies whose specificities have been determined in vertebrates. Crude protein extracts of leech Pontobdella muricata were analysed by Western blotting. The revealed protein band, with 140 kDa molecular weight, was related to dystrophin, utrophin or dystrophin-related protein-2 (DRP2) according to the specificities of the antibodies used to detect them. The immunofluorescence study showed positive immunoreactions in obliquely striated muscle of this hyrudinean. The immunoelectron microscopy study confirmed specific immunogold labelling beneath the sarcolemma of muscle cells. We thus assume that this protein is an invertebrate dystrophin-like product that is referred to as IDLp140. The potential functions of this invertebrate dystrophin-like protein in invertebrate muscles are discussed relative to previous data in vertebrate tissues.

Dystrophin and utrophin complexed with different associated proteins in cardiac Purkinje fibres.

Abnormal dystrophin expression is directly responsible for Duchenne and Becker muscular dystrophies. In skeletal muscle, dystrophin provides a link between the actin network and the extracellular matrix via the dystrophin-associated protein complex. In mature skeletal muscle, utrophin is a dystrophin-related protein localized mainly at the neuromuscular junction, with the same properties as dystrophin in terms of linking the protein complex. Utrophin could potentially overcome the absence of dystrophin in dystrophic skeletal muscles. In cardiac muscle, dystrophin and utrophin were both found to be present with a distinct subcellular distribution in Purkinje fibres, i.e. utrophin was limited to the cytoplasm, while dystrophin was located in the cytoplasmic membrane. In this study, we used this particular characteristic of cardiac Purkinje fibres and demonstrated that associated proteins of dystrophin and utrophin are different in this structure. We conclude, contrary to skeletal muscle, dystrophin-associated proteins do not form a complex in Purkinje fibres. In addition, we have indirect evidence of the presence of two different 400 kDa dystrophins in Purkinje fibres.

Utrophin and dystrophin-associated glycoproteins in normal and dystrophin deficient cardiac muscle.

In this study, various members of the dystrophin family (dystrophin, the short dystrophin product Dp 71, utrophin and DRP2), and different members of the dystrophin-associated glycoprotein (DAG) complex (beta-dystroglycan, alpha-, beta-, gamma- and delta-sarcoglycans) were localized in bovine cardiac muscle using a battery of specific antibodies. We have established that dystrophin is exclusively associated with beta-dystroglycan and both alpha- and delta-sarcoglycans in cardiac muscle cell membranes. In contrast, utrophin is a specific component of intercalated disks together with beta- and gamma-sarcoglycans, while beta-dystroglycan, alpha- and delta-sarcoglycans are not present. Dp 71 is mainly localized at the T tubule transverse area. In dystrophin deficient cardiac muscle, utrophin and beta-sarcoglycan were observed in intercalated disks and at the sarcolemma of each cardiocyte. Our results revealed that complexes of associated glycoproteins differ in cardiac muscle when associated with dystrophin or utrophin. Despite the described sequence homologies between dystrophin and utrophin, the present results indicate that these proteins have different roles in some specific cardiac cell areas.

Expression patterns of dystrophin products, especially of apodystrophin-1/Dp71, in the neural retina of Amphibian urodele Pleurodeles waltl.

The expression patterns of the DMD (Duchenne Muscular Dystrophy) gene products, especially of Dp71 (apodystrophin-1) were investigated by immunofluorescence and immunoblotting in the retina of the Amphibian urodele Pleurodeles waltl. H-5A3 monoclonal antibody (mAb), directed against the C-terminal region of dystrophin/utrophin, and 5F3 mAb, directed against the last 31 amino acids of dystrophin and specific of Dp71, were used. Western blot analyses with H-5A3 mAb revealed distinct dystrophin-family isoforms in adult newt retinal extracts: a doublet 400-420 kDa, Dp260 isoform, a protein at about 120 kDa, and a diffuse zone at 70-80 kDa, which might correspond to Dp71. Reactivity with H-5A3 mAb appeared nearly restricted to the outer plexiform synaptic layer. On the other hand, Dp71-specific 5F3 mAb recognized trhee polypeptide bands at 70-80, 60-65 and 50-55 kDa in adult newt retina corresponding most probably to alternative spliced isoforms of Dp71. In immunohistochemistry by conventional epifluorescence microscopy, 5F3 labeling was mainly observed in the plexiform layers, the outer nuclear layer, and the photoreceptor inner segments, especially at the myoid regions. Analysis by confocal scanning laser microscopy (CSLM) revealed that 5F3 labeling was, in addition, present in the pigmented epithelium and the inner nuclear layer. Furthermore, CSLM showed that 5F3 staining at the myoids was concentrated at discrete domains underneath the plasma membrane. Our findings raised the question concerning the functional significance of Dp71 isoforms, especially at the myoid where Dp71 was detected for the first time, although it occurred here highly expressed. Putative role(s) played in this retinal compartment and other ones by Dp71 and/or other dystrophin isoforms were discussed.

Involvement of the N-terminal region of the human mineralocorticoid receptor hormone-binding domain in agonist and antagonist binding as revealed by a new monoclonal antibody.

To gain a better understanding of the mechanism of binding to the human mineralocorticoid receptor (hMR), we developed a new monoclonal antibody (mAb) raised against the hormone-binding domain (HBD). For this purpose, mice were immunized with a fusion protein including the sequence Thr729-Lys984 of hMR. After ELISA screening, mAb 18C7 was selected for its specificity towards the HBD. This antibody recognized both the denatured and native MR forms, as well as the hetero-oligomeric MR form and the transformed MR state. By using several HBD subfragments, the mAb 18C7 epitope was located in the N-terminal region of the HBD from Thr729 to Leu765. We then studied the effect of the antibody on aldosterone and progesterone binding to the hMR. When 18C7 was incubated with liganded MR, it was able to partly displace (20%) the hormone from its binding site. When 18C7 was incubated with MR before aldosterone or progesterone, the antibody inhibited 75-80% of the binding. The effect of 18C7 on the binding was similar with both hormones. A sucrose gradient analysis indicated the simultaneous presence of two kinds of receptor complexes: the steroid-MR complex and the antibody-MR complex. After its associated proteins, especially the heat-shock protein hsp90, had been cross-linked with the hMR by dimethylpimelimidate, 18C7 was still able to react with the receptor. Our results indicated that the epitope recognized by 18C7 was directly implicated in hormone binding. The lack of steroid binding of HBD mutants with the Thr729-Leu765 sequence deleted [Jalaguier, Mesnier, Léger and Auzou (1996) J. Steroid Biochem. Mol. Biol. 57, 43-50] supports this hypothesis. Because of the similar behaviours of aldosterone and progesterone, we conclude that the N-terminal Thr729-Leu765 region of the HBD is similarly involved in the binding of both hormones.

Different utrophin and dystrophin properties related to their vascular smooth muscle distributions.

Monoclonal antibodies used to distinguish between dystrophin and utrophin were systematically applied to skeletal muscles containing arteries and veins. Small arteries were found to contain long forms of both utrophin and dystrophin, while small veins contained only long forms of utrophin. In addition, all sizes of vascular smooth muscles were demonstrated to contain another related Mr 80 kDa protein (possibly a short utrophin transcript). Regardless of their tissue distributions, we assumed that each of these molecules had distinct properties, i.e. dystrophin with a mechanical function and utrophin with an architectural function. This difference in the roles of dystrophin and utrophin could reduce the efficiency of protection against muscle membrane degeneration when utrophin overexpression is programmed.

Expression of a new M(r) 70-kDa dystrophin-related protein in the axon of peripheral nerves from Torpedo marmorata.

By comparison with localizations of dystrophin family products in rabbit peripheral nerves, we investigated the potential existence and distribution of similar products in peripheral nerves from Torpedo marmorata. In immunofluorescence studies, a specific set of monoclonal antibodies directed against dystrophin family proteins clearly stained a thin rim surrounding each Schwann cell-axon unit both in T. marmorata and rabbit peripheral nerves. In contrast when using the dystrophin/utrophin monoclonal H'3E7 antibody, we found a clear difference between rabbit and T. marmorata peripheral nerves according to fluorescent labeling detected within Torpedo nerve axons. Further differences were noted following western blot analyses of T. marmorata peripheral nerve extracts, highlighting the presence of a new and specific M(r) 70-kDa protein band belonging to the dystrophin family, which is localized within axons in addition to: (1) an M(r)400-kDa protein band detected with dystrophin/utrophin antibodies; and (2) an M(r) 116-kDa doublet protein band corresponding to Dp116 and Up116 isoforms. All of these products, detected according to the specificities of the monoclonal antibodies used, are discussed in terms of their potential identities as short and long dystrophin or utrophin mammalian products.

Presence of long and short dystrophin and/or utrophin products in Torpedo marmorata peripheral nerves.

Peripheral nerves from rabbit and Torpedo marmorata were comparatively analyzed for the presence of short dystrophin products. Western blot analyses of Torpedo marmorata peripheral nerve extracts revealed the existence of three proteins belonging to the dystrophin family: a M(r) 400 kDa protein band detected with dystrophin/utrophin, dystrophin-specific and Torpedo utrophin-specific antibodies, a molecule identified as Dp116 and, for the first time at the protein level, a new protein probably corresponding to Up116. All of these products were carefully identified according to the specificities of the monoclonal antibodies used. In immunofluorescence studies, clear staining of the thin rim surrounding each Schwann cell-axon unit was observed in both Torpedo marmorata and rabbit peripheral nerves, showing colocalization of all of these molecules. Their potential functions were discussed in comparison to similar products found in rabbit peripheral nerves.

Re-evaluation of the distributions of dystrophin and utrophin in sciatic nerve.

Differential expression of proteins belonging to the dystrophin family was analysed in peripheral nerves. In agreement with previous reports, no full-size dystrophin was detectable, only Dp116, one of the short dystrophin products of the Duchenne muscular dystrophy (DMD) gene. We used specific monoclonal antibodies to fully investigate the presence of utrophin, a dystrophin homologue encoded by a gene located on chromosome 6q24. Evidence is presented here of the presence of two potential isoforms of full-length utrophin in different nerve structures, which may differ by alternative splicing of the 3'-terminal part of the utrophin gene according to the specificities of the monoclonal antiobodies used. One full-length utrophin was co-localized with Dp116 in the sheath around each separate Schwann cell-axon unit, but the other utrophin isoform was found to be perineurium-specific. We also highlighted a potential 80 kDa utrophin-related protein. The utrophin distribution in peripheral nerves was re-evaluated and utrophin isoforms were detected at the protein level. This preliminary indication will require more concrete molecular evidence to confirm the presence of these two utrophin isoforms as well as the potential 80 kDa utrophin isoform, but the results strongly suggest that each isoform must have a specialized role and function within each specific nervous structure.

Dystrophin, the protein that promotes membrane resistance.

Deficiency of dystrophin, a 427-kDa subsarcolemma membrane protein, is responsible for Duchenne muscular dystrophy. The function of this protein is not clear but its subcellular distribution suggests that it is an important link between the cytoskeleton and the extracellular matrix, thus maintaining membrane integrity. The N-terminus of dystrophin was shown to bind actin in vivo and in vitro via two major actin binding sites. The role of dystrophin/actin interactions has been investigated and the results presented here demonstrate for the first time that the N-terminal part of dystrophin is able (i) to interact with G-actin monomers, and (ii) to slowly promote G->F actin transformation. This conversion was shown to be stimulated the presence of calmodulin in a calcium dependent manner. This is evidence that dystrophin is an anchor protein for actin involved in the control of membrane cell shape deformation and developing a calmodulin-calcium induced F-actin network, thus stiffening the myotube membrane cytoskeleton.