Division of Genetics and Genomics, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
Department of Pediatrics, Division of Neurology at Children's of Alabama, 1900 University Blvd, Birmingham, AL, 35294, USA.
Adv Biol (Weinh). 2023 Dec;7(12):e2300157. doi: 10.1002/adbi.202300157. Epub 2023 Jul 12.
Tetraspanins organize protein complexes at the cell membrane and are responsible for assembling diverse binding partners in changing cellular states. Tetraspanin CD82 is a useful cell surface marker for prospective isolation of human myogenic progenitors and its expression is decreased in Duchenne muscular dystrophy (DMD) cell lines. The function of CD82 in skeletal muscle remains elusive, partly because the binding partners of this tetraspanin in muscle cells have not been identified. CD82-associated proteins are sought to be identified in human myotubes via mass spectrometry proteomics, which identifies dysferlin and myoferlin as CD82-binding partners. In human dysferlinopathy (Limb girdle muscular dystrophy R2, LGMDR2) myogenic cell lines, expression of CD82 protein is near absent in two of four patient samples. In the cell lines where CD82 protein levels are unaffected, increased expression of the ≈72 kDa mini-dysferlin product is identified using an antibody recognizing the dysferlin C-terminus. These data demonstrate that CD82 binds dysferlin/myoferlin in differentiating muscle cells and its expression can be affected by loss of dysferlin in human myogenic cells.
四跨膜蛋白在细胞膜上组织蛋白复合物，并负责在细胞状态发生变化时组装各种结合配偶体。四跨膜蛋白 CD82 是一种有用的细胞表面标志物，可用于预期分离人类成肌祖细胞，其在杜氏肌营养不良症（DMD）细胞系中的表达降低。CD82 在骨骼肌中的功能仍然难以捉摸，部分原因是这种四跨膜蛋白在肌肉细胞中的结合配偶体尚未被鉴定。通过质谱蛋白质组学在人类肌管中寻找 CD82 相关蛋白，鉴定出 dysferlin 和 myoferlin 是 CD82 的结合配偶体。在人类 dysferlinopathy（肢带型肌营养不良症 R2，LGMDR2）成肌细胞系中，4 个患者样本中的 2 个样本中 CD82 蛋白表达几乎不存在。在 CD82 蛋白水平不受影响的细胞系中，使用识别 dysferlin C 末端的抗体鉴定到 ≈72 kDa 小 dysferlin 产物的表达增加。这些数据表明，CD82 在分化的肌肉细胞中与 dysferlin/myoferlin 结合，并且其表达可能受到人类成肌细胞中 dysferlin 缺失的影响。
