The enigmatic endosome – sorting the ins and outs of endocytic trafficking

Naslavsky, Naava; Caplan, Steven H

doi:10.1242/jcs.216499

Cited by 271 publications

(281 citation statements)

References 211 publications

(178 reference statements)

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“…Proteins of the retrograde route to the TGN are in a constant state of flux as they are recycled throughout the endosomal network (14). Consistent with this phenomenon, we observed a strong enrichment for proteins of the endosomal network amongst those affected by golgin-97-mito.…”

Section: Cargo Specific To Golgin-97 and Golgin-245supporting

confidence: 83%

Determining the content of vesicles captured by golgin tethers using LOPIT-DC

Shin

Crook²,

Borgeaud

et al. 2019

Preprint

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The internal organisation of the cell depends on tethers at destination organelles to selectively capture incoming transport vesicles to facilitate SNARE-mediated fusion. The golgin long coiledcoil proteins function as tethers that contributes to this specificity at the Golgi (1). Golgin-97, golgin-245 and GCC88 golgins of the trans-Golgi capture vesicles derived from endosomes, which serve to recycle the critical Golgi machinery required to deliver lysosomal hydrolases and to maintain exocytosis. Retrograde trafficking from endosomes to the trans-Golgi network (TGN) is a complex process that involves the sorting of transmembrane cargo proteins into distinct transport vesicles by adaptors from multiple pathways. The content of these distinct vesicles, which golgin they target and the factors that mediate this targeting are not well understood. The major challenges that have limited advances in these areas is the transient nature of vesicle tethering, and the redundancies in their mechanisms that confound experimental dissection. To gain better insight into these problems, we performed organelle proteomics using the Localisation of Organelle Proteins by Isotope Tagging after Differential ultraCentrifugation (LOPIT-DC) method on a system in which an ectopic golgin causes vesicles to accumulate in a tethered state (2). By incorporating Bayesian statistical modelling into our analysis (3), we determined that over 45 transmembrane proteins and 51 peripheral membrane proteins of the endosomal network are on vesicles captured by golgin-97, including known cargo and components of the clathrin/AP-1, retromer-dependent and -independent transport pathways. We also determined a distinct class of vesicles shared by golgin-97, golgin-245 and GCC88 that is enriched in TMEM87A, a multi-pass transmembrane protein of unknown function that has previously been implicated in endosome-to-Golgi retrograde transport (4). Finally, we categorically demonstrate that the vesicles that these golgins capture are retrograde transport vesicles based on the lack of enrichment of lysosomal hydrolases in our LOPIT-DC data, and from correlative light electron tomography images of spherical vesicles captured by golgin-97. Together, our study demonstrates the power of combining LOPIT-DC with Bayesian statistical analysis in interrogating the dynamic spatial movement of proteins in transport vesicles.

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Section: Cargo Specific To Golgin-97 and Golgin-245supporting

confidence: 83%

Determining the content of vesicles captured by golgin tethers using LOPIT-DC

Shin

Crook²,

Borgeaud

et al. 2019

Preprint

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“…In addition to autophagy as described above, lysosome receives cargos from other processes including endocytosis through the endocytic pathway. Briefly, following endocytosis, internalized cargos first enter the early endosomes (EE) where the cargos are sorted for two destinations: they are either retrieved for recycling to the plasma membrane/the secretory pathway, or are delivered to the late endosome (LE) and then fuse with lysosome for degradation [20,21]. The main biological functions of the endocytic pathway are for retrieval and recycling of internalized cargo proteins, and such functions are known to play critical roles in the pathology of important human diseases, in particularly neurodegenerative diseases and viral infection [22,23].…”

Section: Brief Introduction Of the Autophagy And The Endocytic Pathwaymentioning

confidence: 99%

Targeting the Endocytic Pathway and Autophagy Process as a Novel Therapeutic Strategy in COVID-19

Yang¹,

Shen²

2020

Int. J. Biol. Sci.

400

444

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Coronaviruses (CoVs) are a group of enveloped, single-stranded positive genomic RNA viruses and some of them are known to cause severe respiratory diseases in human, including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the ongoing coronavirus disease-19 (COVID-19). One key element in viral infection is the process of viral entry into the host cells. In the last two decades, there is increasing understanding on the importance of the endocytic pathway and the autophagy process in viral entry and replication. As a result, the endocytic pathway including endosome and lysosome has become important targets for development of therapeutic strategies in combating diseases caused by CoVs. In this mini-review, we will focus on the importance of the endocytic pathway as well as the autophagy process in viral infection of several pathogenic CoVs inclusive of SARS-CoV, MERS-CoV and the new CoV named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and discuss the development of therapeutic agents by targeting these processes. Such knowledge will provide important clues for control of the ongoing epidemic of SARS-CoV-2 infection and treatment of COVID-19.

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“…Vesicles derived from these processes are mainly delivered to early endosomes, which are membrane compartments that harbor early endosome antigen 1 (EEA1) and Rab5. In addition, early endosomes are complex sorting compartments in which these and other proteins (eg, other Rabs) segregate into sorting domains of a common organelle or separate organelles that function in parallel . Within these early endosomes, sorting of cargo into vesicular or tubular membrane structures allows traffic of cargo to specific locations.…”

Section: Introductionmentioning

confidence: 99%

Energetic adaptations: Metabolic control of endocytic membrane traffic

Rahmani

Defferrari

Wakarchuk

et al. 2019

Traffic

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Endocytic membrane traffic controls the access of myriad cell surface proteins to the extracellular milieu, and thus gates nutrient uptake, ion homeostasis, signaling, adhesion and migration. Coordination of the regulation of endocytic membrane traffic with a cell's metabolic needs represents an important facet of maintenance of homeostasis under variable conditions of nutrient availability and metabolic demand. Many studies have revealed intimate regulation of endocytic membrane traffic by metabolic cues, from the specific control of certain receptors or transporters, to broader adaptation or remodeling of the endocytic membrane network. We examine how metabolic sensors such as AMP‐activated protein kinase, mechanistic target of rapamycin complex 1 and hypoxia inducible factor 1 determine sufficiency of various metabolites, and in turn modulate cellular functions that includes control of endocytic membrane traffic. We also examine how certain metabolites can directly control endocytic traffic proteins, such as the regulation of specific protein glycosylation by limiting levels of uridine diphosphate N‐acetylglucosamine (UDP‐GlcNAc) produced by the hexosamine biosynthetic pathway. From these ideas emerge a growing appreciation that endocytic membrane traffic is orchestrated by many intrinsic signals derived from cell metabolism, allowing alignment of the functions of cell surface proteins with cellular metabolic requirements. Endocytic membrane traffic determines how cells interact with their environment, thus defining many aspects of nutrient uptake and energy consumption. We examine how intrinsic signals that reflect metabolic status of a cell regulate endocytic traffic of specific proteins, and, in some cases, exert broad control of endocytic membrane traffic phenomena. Hence, endocytic traffic is versatile and adaptable and can be modulated to meet the changing metabolic requirements of a cell.

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The enigmatic endosome – sorting the ins and outs of endocytic trafficking

Cited by 271 publications

References 211 publications

Determining the content of vesicles captured by golgin tethers using LOPIT-DC

Determining the content of vesicles captured by golgin tethers using LOPIT-DC

Targeting the Endocytic Pathway and Autophagy Process as a Novel Therapeutic Strategy in COVID-19

Energetic adaptations: Metabolic control of endocytic membrane traffic

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