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Entity

Name
clathrin-dependent endocytosis
Namespace
go
Namespace Version
20181221
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/73688d6dc24e309fca59a1340dc9ee971e9f3baa/external/go-names.belns

Appears in Networks 6

In-Edges 12

p(HGNC:MAPT) positiveCorrelation bp(GO:"clathrin-dependent endocytosis") View Subject | View Object

In the case of soluble monomeric or small oligomeric tau protein, the endocytosis appears to be clathrin-dependent (reviewed in [169]). In contrast, larger aggregates of tau could bind heparin in the extracellular matrix and be internalized through macropinocytosis [170]. As a result of exocytosis and endocytosis, the spreading of tau can occur in various neurodegenerative diseases (tauopathies) including AD. Three plausible mechanisms of tau spreading are shown schematically in Figure 6. Additionally, it appea rs that microglial cells may facilitate tau propagation by phagocytosis and exocytosis of tau protein [171]. PubMed:26751493

complex(p(HBP:"AP-2 complex"), p(HGNCGENEFAMILY:"Clathrin subunits")) positiveCorrelation bp(GO:"clathrin-dependent endocytosis") View Subject | View Object

Phosphatidylinositol binding clathrin assembly protein, PICALM (aka CALM) assembles adaptor protein-2 (AP-2) to clathrin, thus participating in clathrin-mediated endocytosis. We have previously reported that the level of full-length PICALM is decreased in AD brains; PICALM was co-localised with phosphorylated tau in NFTs and in granulovacuolar degenerations (GVDs) in the brains of AD patients and of individuals with Down syndrome but was not observed in amyloid plaques (Ando et al., 2013). PubMed:27260836

Appears in Networks:

p(HGNC:PICALM) increases bp(GO:"clathrin-dependent endocytosis") View Subject | View Object

A recent line of work revealed Aβ-promoting function of PICALM by demonstrating that PICALM depletion decreased Aβ generation through disrupting clathrin-mediated endocytosis and internalization of γ-secretase [99,100]. PubMed:29758300

a(HBP:"Q82 aggregates") decreases bp(GO:"clathrin-dependent endocytosis") View Subject | View Object

However, CME was substantially reduced in cells con- taining Q82 aggregates (Fig. 1 B , arrows), with quantification of internalized transferrin fluorescence showing a 63 ± 11% reduction in aggregate-containing cells compared with cells expressing soluble Q19 or Q82 (Fig. 1 C ). PubMed:24706768

a(HBP:"huntingtin aggregates") decreases bp(GO:"clathrin-dependent endocytosis") View Subject | View Object

CME inhibition was also observed in cells containing aggregated forms of polyQ- expanded Htt exon 1 (Htt Q53); these cells exhibited 50 ± 15% reduced levels of internalized transferrin compared with cells with soluble Htt Q23 or Htt Q53 protein (Fig. S2 A–C ). PubMed:24706768

a(HBP:"huntingtin aggregates") decreases bp(GO:"clathrin-dependent endocytosis") View Subject | View Object

In contrast, there was a marked reduction in CME in neurons containing mutant Htt exon 1 Q73-CFP aggregates compared with nonexpressing cells (Fig. 5 B , Center ; quantification in Fig. 5 D ); PubMed:24706768

p(HGNC:HSPA8) increases bp(GO:"clathrin-dependent endocytosis") View Subject | View Object

Importantly, aggregate-driven CME inhibition is reversible and can be rescued by nominally increasing HSC70 levels. PubMed:24706768

p(HGNC:HSPA8) increases bp(GO:"clathrin-dependent endocytosis") View Subject | View Object

Although internalized transferrin levels remained un- changed in cells with near-normal amounts of HSC70, cells with over a 50% reduction in HSC70 expression had significant CME inhibition (compare Fig. 2 E and D ), with a 51 ± 17% decrease in internalized transferrin fluorescence compared with nondepleted cells. PubMed:24706768

p(HGNC:SOD1, var("p.Ala4Val")) decreases bp(GO:"clathrin-dependent endocytosis") View Subject | View Object

Down- regulation of CME was not limited to polyQ-induced aggre- gation; cells with aggregated mutant SOD1 A4V also exhibited a 50 ± 10% decrease in levels of internalized transferrin com- pared with cells expressing the soluble WT or mutant protein (Fig. 1 E–G ). PubMed:24706768

path(MESH:"Protein Aggregation, Pathological") decreases bp(GO:"clathrin-dependent endocytosis") View Subject | View Object

Here, we show that diverse disease-associated aggregates se- quester the highly abundant major chaperone heat shock cognate protein 70 (HSC70) to the point of functional collapse of an essential cellular process, clathrin-mediated endocytosis (CME). PubMed:24706768

Out-Edges 4

bp(GO:"clathrin-dependent endocytosis") increases deg(p(HGNC:APP)) View Subject | View Object

Moreover, internalization of APP from the cell surface for endosomal/lysosomal degradation can be mediated by clathrin PubMed:21214928

bp(GO:"clathrin-dependent endocytosis") positiveCorrelation p(HGNC:MAPT) View Subject | View Object

In the case of soluble monomeric or small oligomeric tau protein, the endocytosis appears to be clathrin-dependent (reviewed in [169]). In contrast, larger aggregates of tau could bind heparin in the extracellular matrix and be internalized through macropinocytosis [170]. As a result of exocytosis and endocytosis, the spreading of tau can occur in various neurodegenerative diseases (tauopathies) including AD. Three plausible mechanisms of tau spreading are shown schematically in Figure 6. Additionally, it appea rs that microglial cells may facilitate tau propagation by phagocytosis and exocytosis of tau protein [171]. PubMed:26751493

bp(GO:"clathrin-dependent endocytosis") positiveCorrelation complex(p(HBP:"AP-2 complex"), p(HGNCGENEFAMILY:"Clathrin subunits")) View Subject | View Object

Phosphatidylinositol binding clathrin assembly protein, PICALM (aka CALM) assembles adaptor protein-2 (AP-2) to clathrin, thus participating in clathrin-mediated endocytosis. We have previously reported that the level of full-length PICALM is decreased in AD brains; PICALM was co-localised with phosphorylated tau in NFTs and in granulovacuolar degenerations (GVDs) in the brains of AD patients and of individuals with Down syndrome but was not observed in amyloid plaques (Ando et al., 2013). PubMed:27260836

Appears in Networks:

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.