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Myofibrillar myopathy (MFM) describes a group of hereditary myopathies pathologically characterized as markedly disorganized myofibrils with cytoplasmic inclusions. Seven disease-related genes have been identified, including DES, CRYAB, MYOT, ZASP, FLNC, BAG3, and FHL1, all of which encode proteins closely related to Z-line. MFM often occurs via autosomal dominant inheritance, but autosomal recessive, or X-linked, forms are also seen. The majority of Japanese patients have no family history. Clinical symptoms of MFM are quite variable. The age at onset ranges from infancy to the eighth decade of life. Some patients show limb girdle muscle involvement, whereas others show distal myopathy. Patients who have cardiomyopathy with no obvious muscle weakness are also seen. Skeletal muscles from MFM patients contain cytoplasmic inclusions called cytoplasmic or spheroid bodies. Immunohistochemically, cytoplasmic accumulations of various proteins are commonly seen, including Z-line proteins such as desmin, αB-crystallin, and myotilin; membrane proteins such as dystrophin and sarcoglycans; heat shock proteins; and ubiquitin. We review the clinical, pathological, and genetic characteristics of MFM patients, including those from our recent study results. Despite intensive mutation screening, about 70% of MFM patients in our series had no mutation in the known causative genes. The identification of novel disease-related genes and the development of efficient diagnostic tools are urgently needed, as is the elucidation of the pathomechanism of myofibril disorganization as a possible target for new treatments.

During the embryonic development, neurons migrate from their origin to their final position. Control of neuronal migrations is critical for formation of the complex architecture of the central nervous system. In the developing central nervous system, there are two major patterns of neuronal migrations. One is radial migration and the other is tangential migration. In radial migration, migrating cells move along radial fibers that are processes of radial glial cells. Contact between radial glial cells and migrating cells has been supposed to control radial migration. In tangential migration, some tracts of neuronal migrations are controlled by chemokines. Neuronal migration utilizes its own migratory strategies, such as cell-cell contact with radial glial cells as well as common principles of cell migration like chemoattractants. As cell migrations reflect cytoskeletal changes in the cells, external cues like chemoattractants and cell adhesion finally influence the structure of cytoskeleton in migrating neurons. We summarize previous studies on cell migration and discuss specific mechanisms of neural migration in this review.

C-kinase is an intracellular protein kinase which is activated by Ca2+ and phospholipid, and plays a crucial role in signal transduction and cell proliferation. To clarify the possibility that C-kinase regulates the growth or maturation of placental tissues, I have purified C-kinase from human placental chorion by sequential column chromatography, determined the substrate specificity of the purified C-kinase, and then investigated the effects of various hormones on the phosphorylation of placental chorionic membrane proteins. The results were as follows: 1) pH optimum of C-kinase was 8.0, apparent Ka for Ca2+ was 1 X 10(-5) M and Ka for phosphatidylserine was 80 micrograms/ml. 2) One of the cytoskeletal proteins, filamin, was phosphorylated specifically by the purified C-kinase. 3) The C-kinase activity increased with placental growth. The enzyme activity in the 3rd. trimester of pregnancy was 5 times higher than that in the 1st. trimester. 4) C-kinase activity was inhibited by hCG and markedly stimulated by DHA or DHAS. These results suggest that C-kinase is involved in the specific functions of the placenta.