Sarcolemmopathy: Muscular dystrophies with cell membrane defects

In this article, we review the molecular pathology of muscular dystrophies caused by defects of proteins located within or near cell membranes. These disorders include Bethlem myopathy, merosinopathy, dystrophinopathy, sarcog lycanopathies, integrinopathy, dysferlinopathy and caveolinopathy. We refer to these diseases collectively as sarcolemmopathy. Here, we describe the b iological functions of these proteins in the context of muscular contractio ns and their roles in the infrastructure of muscle; defects of muscle infra structures cause those diseases. As an example, in dystrophinopathy, cell membranes have mechanical defects due to the absence of dystrophin. Cracks of the cell membrane induced by mu scle contraction may allow the influx and efflux of substances that trigger muscle cell degeneration. However, such cracks may be resealed on relaxati on. In addition, dystrophinopathy causes secondary defects of various dystr ophin-associated proteins suggesting that defects in cell signaling partici pate in the pathologic process, With regard to other sarcolemmopathies, we discuss pathological mechanisms based on available data.