Manta Panagiota, Terzis Gerasimos, Papadimitriou Constantinos, Kontou Chrysanthi, Vassilopoulos Demetris
Department of Neurology, Medical School, University of Athens, V. Sofias 74, 11528 Athens, Greece.
Acta Neuropathol. 2004 Jun;107(6):546-52. doi: 10.1007/s00401-004-0851-1. Epub 2004 Apr 14.
Emerin is an inner nuclear membrane protein that is mutated or not expressed in patients with X-linked Emery-Dreifuss muscular dystrophy (X-EDMD/EMD). Cytoplasmic localization of emerin in cultured cells or tissues has been reported, although this remains a controversial issue. Tubular aggregates (TAs) are pathological structures seen in the sarcoplasm of human skeletal muscle fibers in various disorders. The TAs derive from the sarcoplasmic reticulum (SR) and represent, probably, an adaptive response of the SR to various insults to the muscle fibers. In the present study, we present immunohistochemical evidence of emerin expression in TAs. Muscle biopsies with tubular aggregates from four male, unrelated patients were studied. The percentage of muscle fibers containing TAs varied between 5 and 20%. Routine histochemistry revealed intense reaction of TAs with NADH-TR, AMPDA, and NSE, but not with COX, SDH, myosin ATPase (pH 9.4, 4.3, 4.6), PAS, and Oil red O staining. Immunohistochemical study revealed strong immunostaining of TAs with antibodies against emerin and 7 SERCA2-ATPase. Immunostaining of TAs was also seen with antibodies against heat shock protein and dysferlin, but not with antibodies to lamin A, dystrophin, adhalin, beta, gamma, delta sarcoglycans, and merosin. These results suggest that emerin, an inner nuclear membrane protein, is present at the TAs. The interpretation and significance of this finding is discussed in relation to experimental data suggesting that normal emerin localization at the inner nuclear membrane depends on lamin A and mutations in the N-terminal domain of emerin cause mislocalization of the protein to the sarcoplasmic membranes.
Emerin是一种内核膜蛋白，在患有X连锁Emery-Dreifuss肌营养不良症（X-EDMD/EMD）的患者中发生突变或不表达。尽管这仍然是一个有争议的问题，但已有报道称Emerin在培养细胞或组织中存在于细胞质中。管状聚集体（TAs）是在各种疾病的人类骨骼肌纤维肌浆中可见的病理结构。TAs来源于肌浆网（SR），可能代表SR对肌纤维各种损伤的适应性反应。在本研究中，我们提供了Emerin在TAs中表达的免疫组织化学证据。对来自四名无亲缘关系男性患者的带有管状聚集体的肌肉活检组织进行了研究。含有TAs的肌纤维百分比在5%至20%之间。常规组织化学显示TAs与NADH-TR、AMPDA和NSE反应强烈，但与COX、SDH、肌球蛋白ATP酶（pH 9.4、4.3、4.6）、PAS和油红O染色无反应。免疫组织化学研究显示，针对Emerin和7种SERCA2-ATP酶的抗体对TAs有强烈免疫染色。针对热休克蛋白和dysferlin的抗体也能观察到TAs的免疫染色，但针对核纤层蛋白A、肌营养不良蛋白、整合素、β、γ、δ肌聚糖和merosin的抗体则不能。这些结果表明，一种内核膜蛋白Emerin存在于TAs中。结合实验数据讨论了这一发现的解释和意义，实验数据表明Emerin在内核膜上的正常定位依赖于核纤层蛋白A，并且Emerin N端结构域的突变会导致该蛋白错误定位于肌浆膜。
