Departments of Biology and of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, United States of America; School of Public Health, Harvard Medical School, Boston, Massachusetts, United States of America.
Departments of Biology and of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
PLoS One. 2014 Apr 4;9(4):e93680. doi: 10.1371/journal.pone.0093680. eCollection 2014.
It is increasingly recognized that non-erythroid spectrins have roles remote from the plasma membrane, notably in endomembrane trafficking. The large spectrin isoform, βH, partners with Annexin B9 to modulate endosomal processing of internalized proteins. This modulation is focused on the early endosome through multivesicular body steps of endocytic processing and loss of either protein appears to cause a traffic jam before removal of ubiquitin at the multivesicular body. We previously reported that βH/Annexin B9 influenced EGF receptor signaling. While investigating this effect we noticed that mSptiz, the membrane bound precursor of the secreted EGF receptor ligand sSpitz, is located in striking intrusions of the nuclear membrane. Here we characterize these structures and identify them as 'cytoplasmic capes', which were previously identified in old ultrastructural studies and probably coincide with recently recognized sites of non-nuclear-pore RNA export. We show that cytoplasmic capes contain multiple endosomal markers and that their existence is dependent upon βH and Annexin B9. Diminution of these structures does not lead to a change in mSpitz processing. These results extend the endosomal influence of βH and its partner Annexin B9 to this unusual compartment at the nuclear envelope.
人们越来越认识到,非红细胞 spectrin 具有远离质膜的作用,特别是在细胞内膜运输中。大型 spectrin 同种型βH 与 Annexin B9 结合,调节内化蛋白的内体处理。这种调节集中在早期内涵体上,通过胞吞作用的多泡体步骤,并且这两种蛋白质的丢失似乎在多泡体处除去泛素之前导致了交通堵塞。我们之前报道过βH/Annexin B9 影响 EGF 受体信号。在研究这种影响时,我们注意到,EGF 受体配体 sSpitz 的膜结合前体 mSptiz 位于核膜的显著突起中。在这里,我们对这些结构进行了特征描述,并将其鉴定为“细胞质披肩”,这些结构在以前的超微结构研究中已经被发现,可能与最近公认的非核孔 RNA 输出位点相吻合。我们表明细胞质披肩包含多个内体标记物,并且它们的存在依赖于βH 和 Annexin B9。这些结构的减少不会导致 mSpitz 处理的改变。这些结果将βH 及其伴侣 Annexin B9 的内体影响扩展到核膜的这个不寻常隔室。