Cytoplasmic Capes Are Nuclear Envelope Intrusions That Are Enriched in Endosomal Proteins and Depend upon

It is increasingly recognized that non-erythroid spectrins have roles remote from the plasma membrane, notably in endomembrane trafficking. The large spectrin isoform, bH, 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 bH/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 bH and Annexin B9. Diminution of these structures does not lead to a change in mSpitz processing. These results extend the endosomal influence of bH and its partner Annexin B9 to this unusual compartment at the nuclear envelope. Citation: Wu J, Bakerink KJ, Evangelista ME, Thomas GH (2014) Cytoplasmic Capes Are Nuclear Envelope Intrusions That Are Enriched in Endosomal Proteins and Depend upon bH-Spectrin and Annexin B9. PLoS ONE 9(4): e93680. doi:10.1371/journal.pone.0093680 Editor: Alexander F. Palazzo, University of Toronto, Canada Received October 16, 2013; Accepted March 7, 2014; Published April 4, 2014 Copyright: 2014 Wu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by grant #MCB-1122013 from the National Science Foundation (www.nsf.gov). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected]