To degrade or not to degrade: mechanisms and significance of endocytic recycling

Cullen, Peter J.; Steinberg, Florian

doi:10.1038/s41580-018-0053-7

Cited by 450 publications

(498 citation statements)

References 250 publications

(216 reference statements)

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“…On the other hand, lysosome is also a key component of the endocytic pathway, also termed as the endolysosomal network [20] (Figure 1). In addition to autophagy as described above, lysosome receives cargos from other processes including endocytosis through the endocytic pathway.…”

Section: Brief Introduction Of the Autophagy And The Endocytic Pathwaymentioning

confidence: 99%

“…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%

See 1 more Smart Citation

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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Section: Brief Introduction Of the Autophagy And The Endocytic Pathwaymentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…Many integral membrane proteins contain linear sequence motifs that determine endocytosis, recycling or degradation (Bonifacino and Traub, 2003;Cullen and Steinberg, 2018). However, sequence inspection did not reveal canonical sorting motifs in the cytoplasmic regions of GDE2, such as tyrosine-or leucine-based motifs.…”

Section: C-terminal Tail Truncations Of Gde2 Disclose Unique Regulatomentioning

confidence: 98%

Sequence-dependent trafficking of GDE2, a GPI-specific phospholipase promoting neuronal differentiation

Salgado-Polo

Veen

Broek

et al. 2019

Preprint

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GDE2 is a six-transmembrane glycerophosphodiesterase with phospholipase D-like activity that cleaves select glycosylphosphatidylinositol (GPI)-anchored proteins and thereby influences biological signaling cascades. GDE2 promotes neuronal differentiation cell-autonomously through glypican cleavage and is a prognostic marker in neuroblastoma, while GDE2 deficiency causes progressive neurodegeneration in mice and developmental defects in zebrafish.However, the regulation of GDE2 remains unclear. Here we show that in undifferentiated neuronal cells, GDE2 undergoes constitutive internalization and traffics back along both fast and slow recycling routes, while a small percentage is sorted to late endosomes. GDE2 trafficking is dictated by distinctive C-terminal tail sequences that determine secretion, endocytosis and recycling preference, respectively, and thereby regulate GDE2 function both positively and negatively. Our study reveals the sequence determinants of GDE2 trafficking and surface localization, and provides insight into the control of GPI-anchored protein activities with potential implications for nervous system disorders associated with impaired trafficking and beyond.

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“…The retromer core initiates cargo recognition and mediates the engagement of other factors that enable proper endocytic trafficking (Cullen and Steinberg, 2018). However, the differential requirements of each protein within the heterotrimer, including VPS35, VPS26, and VPS29, remain incompletely defined.…”

Section: Vps29 Is Required For Retromer Recruitment Via Rab7 and Tbc1d5mentioning

confidence: 99%

Retromer subunit, VPS29, regulates synaptic transmission and is required for endolysosomal function in the aging brain

Ojelade

Li‐Kroeger

et al. 2019

Preprint

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AbstractRetromer, including Vps35, Vps26, and Vps29, is a protein complex responsible for recycling proteins within the endolysosomal pathway. Although implicated in both Parkinson’s and Alzheimer’s disease, our understanding of retromer function in the adult brain remains limited, in part because Vps35 and Vps26 are essential for development. In Drosophila, we find that Vps29 is dispensable for embryogenesis but required for retromer function in aging adults, including for synaptic transmission, survival, and locomotion. Unexpectedly, in Vps29 mutants, Vps35 and Vps26 proteins are normally expressed and associated, but retromer is mislocalized from neuropil to soma with the Rab7 GTPase. Further, Vps29 phenotypes are suppressed by reducing Rab7 or overexpressing the GTPase activating protein, TBC1D5. With aging, retromer insufficiency triggers progressive endolysosomal dysfunction, with ultrastructural evidence of impaired substrate clearance and lysosomal stress. Our results reveal the role of Vps29 in retromer localization and function, highlighting requirements for brain homeostasis in aging.Impact StatementVps29 promotes retromer localization in the adult Drosophila brain, engaging Rab7 and TBC1D5, and its loss triggers age-dependent neuronal impairments in endolysosomal trafficking and synaptic transmission.

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To degrade or not to degrade: mechanisms and significance of endocytic recycling

Cited by 450 publications

References 250 publications

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

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

Sequence-dependent trafficking of GDE2, a GPI-specific phospholipase promoting neuronal differentiation

Retromer subunit, VPS29, regulates synaptic transmission and is required for endolysosomal function in the aging brain

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