We have recently identified a CRM1-dependent nuclear export signal (NES) in the COOH-terminal moiety of Dok-7 and demonstrated that the NES as well

as the SH2 target motifs are critical for MuSK activation in myotubes (31).
Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive disease, found exclusively in Japan (1, 2). The gene responsible is fukutin coding a protein of 461 amino acids (3). FCMD is classified into a group of congenital muscular dystrophies accompanying central nervous system (CNS) and ocular lesions. Muscle-eye-brain disease (MEB) and Walker-Warburg syndrome (WWS) are also included in this group (1). The CNS lesions are generally Inhibitors,research,lifescience,medical characterized by cobblestone Inhibitors,research,lifescience,medical lissencephaly, in other words, type II lissencephaly or polymicrogyria. The skeletal muscle of FCMD patients

shows decreased glycosylation of α-dystroglycan (α-DG) (4), one of the components of the dystrophin-glycoprotein complex linking intracellular and extracellular proteins (1, 5). Muscular dystrophies showing a decrease of glycosylated Inhibitors,research,lifescience,medical α-DG are called α-dystroglycanopathy, in which FCMD, MEB, WWS, congenital muscular dystrophy IC (MDC1C), limb girdle muscular dystrophy 2I (LGMD2I) and MDC1D are included (5). Besides fukutin, other genes responsible for α-dystroglycanopathy have been found, e.g., protein O-linked mannose β1,2-N-acetylglucosaminyltransferase (POMGnT1) Inhibitors,research,lifescience,medical in MEB, protein-O-mannosyltransferase 1 (POMT1) and POMT2 in WWS, fukutin-related protein (FKRP) in MDC1C and LGMD2I, and LARGE in MDC1D (5). POMGnT1 has an enzymatic activity for the glycosylation of α-DG (6, 7). Co-expression of POMT1 and POMT2 is required for enzymatic activity (8). Fukutin seems to relate to the glycosylation of α-DG, but its function has not been proven directly. The decreased glycosylation of α-DG has been observed in the CNS of FCMD, as well as in the skeletal muscle, by western blotting and immunohistochemistry (9). In contrast, the expression of DG mRNA appears to be increased in

the cerebrum of FCMD (Fig. ​(Fig.1).1). Inhibitors,research,lifescience,medical Since the CNS is composed of several components such as neurons, glial cells, capillaries Megestrol Acetate and leptomeninges, it is necessary to study which component is involved in the formation of CNS lesions. Figure 1 A) Western blotting using an antibody against glycosylated α-DG (VIA4-1). Bands around 120 kDa are seen in fetal and adult controls, but there are no bands in FCMD patients. B) RT-PCR using the same cases as those in A). DG mRNA is slightly expressed … CNS lesions of FCMD Both in fetal and post-natal FCMD cases, CNS lesions are predominantly observed in the surface areas, represented by cortical dysplasia of the cerebrum and cerebellum (9). Basic structures of the CNS look normal. Adriamycin Maturation of the brain in fetal cases appears to correspond to the gestational age. Distribution and severity of the dysplasia are different from case to case.