A Novel Class of ER Membrane Proteins Regulates ER-Associated Endosome Fission

• Published in: Cell Vol. 175; no. 1; pp. 254 - 265.e14
• Main Authors: Hoyer, Melissa J., Chitwood, Patrick J., Ebmeier, Christopher C., Striepen, Jonathan F., Qi, Robert Z., Old, William M., Voeltz, Gia K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.09.2018
• Subjects: Animals; Calcium Channels; Chlorocebus aethiops; COS Cells; endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - physiology; endosome fission; endosome recycling; Endosomes - metabolism; Endosomes - physiology; Golgi Apparatus - metabolism; HeLa Cells; Humans; membrane contact site; Membrane Proteins - metabolism; Microfilament Proteins - physiology; Microtubules - metabolism; Protein Transport - physiology; membrane contact site; endosome recycling; endosome fission; endoplasmic reticulum
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2018.08.030

Endoplasmic reticulum (ER) membrane contact sites (MCSs) mark positions where endosomes undergo fission for cargo sorting. To define the role of ER at this unique MCS, we targeted a promiscuous biotin ligase to cargo-sorting domains on endosome buds. This strategy identified the ER membrane protein TMCC1, a member of a conserved protein family. TMCC1 concentrates at the ER-endosome MCSs that are spatially and temporally linked to endosome fission. When TMCC1 is depleted, endosome morphology is normal, buds still form, but ER-associated bud fission and subsequent cargo sorting to the Golgi are impaired. We find that the endosome-localized actin regulator Coronin 1C is required for ER-associated fission of actin-dependent cargo-sorting domains. Coronin 1C is recruited to endosome buds independently of TMCC1, while TMCC1/ER recruitment requires Coronin 1C. This link between TMCC1 and Coronin 1C suggests that the timing of TMCC1-dependent ER recruitment is tightly regulated to occur after cargo has been properly sequestered into the bud. [Display omitted] •Targeted BioID identifies new family of ER-endosome MCS proteins termed TMCC•TMCC1 localizes to dynamic ER domains that define the position of endosome fission•TMCC1 regulates ER recruitment to endosome sorting domains for bud fission•Coronin1C at buds is a receptor for TMCC1-dependent ER recruitment to endosomes The timing and location of endosome fission is tightly regulated by TMCC1-mediated ER recruitment to ER-membrane contact to ensure that budding happens only after cargo has been properly sequestered.