TSSC1 is novel component of the endosomal retrieval machinery

Gershlick, David C.; Schindler, Christina; Chen, Yu; Bonifacino, Juan S.

doi:10.1091/mbc.e16-04-0209

Cited by 31 publications

(37 citation statements)

References 60 publications

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“…The results presented here show that kish/TMEM167A, a protein previously associated with vesicle transport and secretion (Gershlick et al, 2016;Wendler et al, 2010), is necessary for glioma growth, both in human cell xenografts and Drosophila models. Mechanistically, kish/TMEM167A downregulation alters the endo-lysosomal system.…”

Section: Discussionmentioning

confidence: 58%

Oncogenic dependence of glioma cells on kish/TMEM167A regulation of vesicular trafficking

Portela

Segura-Collar

Argudo

et al. 2018

Glia

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Genetic lesions in glioblastoma (GB) include constitutive activation of PI3K and EGFR pathways to drive cellular proliferation and tumor malignancy. An RNAi genetic screen, performed in Drosophila melanogaster to discover new modulators of GB development, identified a member of the secretory pathway: kish/TMEM167A. Downregulation of kish/TMEM167A impaired fly and human glioma formation and growth, with no effect on normal glia. Glioma cells increased the number of recycling endosomes, and reduced the number of lysosomes. In addition, EGFR vesicular localization was primed toward recycling in glioma cells. kish/TMEM167A downregulation in gliomas restored endosomal system to a physiological state and altered lysosomal function, fueling EGFR toward degradation by the proteasome. These endosomal effects mirrored the endo/lysosomal response of glioma cells to Brefeldin A (BFA), but not the Golgi disruption and the ER collapse, which are associated with the undesirable toxicity of BFA in other cancers. Our results suggest that glioma growth depends on modifications of the vesicle transport system, reliant on kish/TMEM167A. Noncanonical genes in GB could be a key for future therapeutic strategies targeting EGFR‐dependent gliomas.

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Section: Discussionmentioning

confidence: 58%

Oncogenic dependence of glioma cells on kish/TMEM167A regulation of vesicular trafficking

Portela

Segura-Collar

Argudo

et al. 2018

Glia

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“…EARP is required for the recycling of cargos from recycling endosomes back to the plasma membrane (Schindler, Chen, et al, 2015). EIPR1 was also shown to be required for the endocytic recycling of transferrin in HAP1 cells (Gershlick et al, 2016).…”

Section: Eipr1 Is Required For Earp Function But Not Garp Functionmentioning

confidence: 98%

“…It was recently shown that mammalian EIPR1 interacts with the EARP and GARP complex subunits and functions with EARP in endosomal recycling and with GARP in endosome-Golgi retrograde trafficking (Gershlick et al, 2016;Topalidou et al, 2016).…”

Section: Eipr1 Is Needed For the Localization Of Earp Subunits And Thmentioning

confidence: 99%

“…EIPR1 physically interacts with the EARP complex in rat insulinoma cells (Topalidou et al, 2016). EIPR1 (also named TSSC1) was also independently identified as a physical interactor and functional partner of both the GARP and EARP complexes in human cell lines (Gershlick et al, 2016). Moreover, two mass spectrometry interactome data sets identified EIPR1 as an interactor of EARP subunits in human HEK293T and HeLa cells (Hein et al, 2015;Huttlin et al, 2015).…”

mentioning

confidence: 97%

“…Fluorescence recovery after photobleaching in Eipr1 knockdown cells showed that EIPR1 is required for efficient recruitment of GARP to the TGN (Gershlick et al, 2016).…”

mentioning

confidence: 99%

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EIPR1 controls dense-core vesicle cargo retention and EARP complex localization in insulin-secreting cells

Topalidou

Cattin‐Ortolá

Hummer

et al. 2018

Preprint

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Dense-core vesicles (DCVs) are secretory vesicles found in neurons and endocrine cells. DCVs package and release cargos including neuropeptides, biogenic amines, and peptide hormones. We recently identified the endosome-associated recycling protein (EARP) complex and the EARP-interacting protein EIPR-1 as proteins important for controlling levels of DCV cargos in C. elegans neurons. Here we determine the role of mammalian EIPR1 in insulinoma cells. We find that in Eipr1 KO cells, there is reduced insulin secretion, and mature DCV cargos such as insulin and carboxypeptidase E (CPE) accumulate near the trans-Golgi network and are not retained in mature DCVs in the cell periphery. In addition, we find that EIPR1 is required for the stability of the EARP complex subunits and for the localization of EARP and its association with membranes, but EIPR1 does not affect localization or function of the related Golgiassociated retrograde protein (GARP) complex. EARP is localized to two distinct compartments related to its function: an endosomal compartment and a DCV biogenesis-related compartment. We propose that EIPR1 functions with EARP to control both endocytic recycling and DCV maturation.

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Comparative Genomics for Evolutionary Cell Biology Using AMOEBAE: Understanding the Golgi and Beyond

Barlow

Maciejowski

et al. 2022

Methods in Molecular Biology

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TSSC1 is novel component of the endosomal retrieval machinery

Cited by 31 publications

References 60 publications

Oncogenic dependence of glioma cells on kish/TMEM167A regulation of vesicular trafficking

Oncogenic dependence of glioma cells on kish/TMEM167A regulation of vesicular trafficking

EIPR1 controls dense-core vesicle cargo retention and EARP complex localization in insulin-secreting cells

Comparative Genomics for Evolutionary Cell Biology Using AMOEBAE: Understanding the Golgi and Beyond

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