Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 30, Issue 12, Pages 1377-1389Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E18-11-0698
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Funding
- German Research Foundation (DFG) [SCHL1876/2-1]
- Academy of Finland [1287975]
- Sigrid Juselius Foundation
- Biocenter Finland
- Helsinki Institute of Life Science Fellow's program
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The endoplasmic reticulum (ER) is extensively remodeled during metazoan open mitosis. However, whether the ER becomes more tubular or more cisternal during mitosis is controversial, and dedicated factors governing the morphology of the mitotic ER have remained elusive. Here, we describe the ER membrane proteins REEP3 and REEP4 as major determinants of ER morphology in metaphase cells. REEP3/4 are specifically required for generating the high-curvature morphology of mitotic ER and promote ER tubulation through their reticulon homology domains (RHDs). This ER-shaping activity of REEP3/4 is distinct from their previously described function to clear ER from metaphase chromatin. We further show that related REEP proteins do not contribute to mitotic ER shaping and provide evidence that the REEP3/4 carboxyterminus mediates regulation of the proteins. These findings confirm that ER converts to higher curvature during mitosis, identify REEP3/4 as specific and crucial morphogenic factors mediating ER tubulation during mitosis, and define the first cell cycle-specific role for RHD proteins.
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