Dual function for Tango1 in secretion of bulky cargo and in ER-Golgi morphology
| Autor: | Luis Daniel Rios-Barrera, Maria Leptin, Magdalena M. Baer, Sara Sigurbjörnsdóttir |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Morphology (linguistics) Sec16 GM130 Cell Vesicular Transport Proteins Golgi Apparatus macromolecular substances ERGIC Cell morphology Endoplasmic Reticulum 03 medical and health sciences symbols.namesake 0302 clinical medicine ERES medicine Animals Drosophila Proteins Secretion Secretory pathway Multidisciplinary Chemistry Aryl Hydrocarbon Receptor Nuclear Translocator Cell Biology Golgi apparatus Biological Sciences Endoplasmic Reticulum Stress Cell biology Protein Transport 030104 developmental biology Secretory protein medicine.anatomical_structure Drosophila melanogaster PNAS Plus Mutagenesis Gene Knockdown Techniques symbols Unfolded protein response ER stress 030217 neurology & neurosurgery Function (biology) |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 |
| Popis: | Significance Exporting bulky molecules poses challenges for cells, since the membrane vesicles that transport normal-sized molecules may not be sufficiently large. The protein Tango1 allows transport vesicles to grow much larger to accommodate bulky cargo. It has been puzzling why many smaller cargos also fail to be transported when Tango1 is absent. We show that this is because bulky cargos “clog up” the transport system, resulting in a general traffic jam. Once the blocking, large cargo is removed, the jam resulting from missing Tango1 is resolved, and other cellular stress signals also subside. However, structural defects in the transport system remain, showing that these are due to a direct requirement for Tango1, independent of its function in transport as such. Tango1 enables ER-to-Golgi trafficking of large proteins. We show here that loss of Tango1, in addition to disrupting protein secretion and ER/Golgi morphology, causes ER stress and defects in cell shape. We find that the previously observed dependence of smaller cargos on Tango1 is a secondary effect. If large cargos like Dumpy, which we identify as a Tango1 cargo, are removed from the cell, nonbulky proteins reenter the secretory pathway. Removal of blocking cargo also restores cell morphology and attenuates the ER-stress response. Thus, failures in the secretion of nonbulky proteins, ER stress, and defective cell morphology are secondary consequences of bulky cargo retention. By contrast, ER/Golgi defects in Tango1-depleted cells persist in the absence of bulky cargo, showing that they are due to a secretion-independent function of Tango1. Therefore, maintenance of ER/Golgi architecture and bulky cargo transport are the primary functions for Tango1. |
| Databáze: | OpenAIRE |
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