title: Tango1 spatially organizes ER exit sites to control ER export.
abstract: Exit of secretory cargo from the endoplasmic reticulum (ER) takes place at specialized domains called ER exit sites (ERESs). In mammals, loss of TANGO1 and other MIA/cTAGE (melanoma inhibitory activity/cutaneous T cell lymphoma-associated antigen) family proteins prevents ER exit of large cargoes such as collagen. Here, we show thatDrosophila melanogasterTango1, the only MIA/cTAGE family member in fruit flies, is a critical organizer of the ERES-Golgi interface. Tango1 rings hold COPII (coat protein II) carriers and Golgi in close proximity at their center. Loss of Tango1, present at ERESs in all tissues, reduces ERES size and causes ERES-Golgi uncoupling, which impairs secretion of not only collagen, but also all other cargoes we examined. Further supporting an organizing role of Tango1, its overexpression creates more and larger ERESs. Our results suggest that spatial coordination of ERES, carrier, and Golgi elements through Tango1's multiple interactions increases secretory capacity inDrosophilaand allows secretion of large cargo.
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Min
authors.identifier: 0000-0001-7553-7425
authors.initials: M
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zhi
authors.identifier: 0000-0002-9740-0435
authors.initials: Z
authors.lastname: Feng
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Hongmei
authors.identifier: 0000-0002-9942-4158
authors.initials: H
authors.lastname: Ke
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ying
authors.identifier: 0000-0002-8487-915X
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Tianhui
authors.identifier: 0000-0002-5720-1466
authors.initials: T
authors.lastname: Sun
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Jianli
authors.identifier: 0000-0002-2032-7292
authors.initials: J
authors.lastname: Dai
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Wenhong
authors.identifier: 0000-0003-3934-9309
authors.initials: W
authors.lastname: Cui
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China jose.pastor@biomed.tsinghua.edu.cn.
authors.forename: José Carlos
authors.identifier: 0000-0002-3823-4473
authors.initials: JC
authors.lastname: Pastor-Pareja
mesh_terms: D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D022181:COP-Coated Vesicles / Q000378:metabolism / Q000502:physiology; D004331:Drosophila melanogaster / Q000378:metabolism / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000502:physiology*; D006056:Golgi Apparatus / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D033921:Vesicular Transport Proteins; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator