Department of Cell Biology and Anatomy, School of Medicine, University of Miami, Miami, Florida 33136, USA.
J Cell Physiol. 2010 Apr;223(1):209-14. doi: 10.1002/jcp.22028.
MUC4 is a heterodimeric membrane mucin, composed of a mucin subunit ASGP-1 (MUC4alpha) and a transmembrane subunit ASGP-2 (MUC4beta), which has been implicated in the protection of epithelial cell surfaces. In the rat stratified corneal epithelium Muc4 is found predominantly in the most superficial cell layers. Since previous studies in other tissues have shown that Muc4 is regulated by TGF-beta via a proteosomal degradation mechanism, we investigated the regulation of corneal Muc4 in stratified cultures of corneal epithelial cells. Application of proteosome or processing inhibitors led to increases in levels of Muc4, particularly in the basal and intermediate levels of the stratified cultures. These changes were accompanied by increases in Muc4 ubiquitination, chaperone association and incorporation into intracellular aggresomes. In contrast, treatment with TGF-beta resulted in reduced levels of Muc4, which were reversed by proteosome inhibition. The results support a model in which Muc4 precursor is synthesized in all layers of the corneal epithelium, but Muc4 is degraded in basal and intermediate layers by a proteosomal mechanism at least partly dependent on TGF-beta inhibition of Muc4 processing.
黏蛋白 4 是一种异二聚体膜黏蛋白，由黏蛋白亚基 ASGP-1（MUC4alpha）和跨膜亚基 ASGP-2（MUC4beta）组成，它与上皮细胞表面的保护有关。在大鼠复层角膜上皮中，Muc4 主要存在于最浅层的细胞层中。由于先前在其他组织中的研究表明，Muc4 通过蛋白酶体降解机制被 TGF-β调节，我们研究了角膜上皮细胞的分层培养中角膜 Muc4 的调节。蛋白酶体或加工抑制剂的应用导致 Muc4 水平增加，特别是在分层培养的基底和中间层。这些变化伴随着 Muc4 泛素化、伴侣蛋白结合和纳入细胞内聚集体的增加。相比之下，TGF-β 的处理导致 Muc4 水平降低，而蛋白酶体抑制可逆转这种降低。结果支持这样一种模型，即 Muc4 前体在角膜上皮的所有层中合成，但 Muc4 在前基底和中间层中通过蛋白酶体机制降解，该机制至少部分依赖于 TGF-β 对 Muc4 加工的抑制。
