Disease relevance of Chc

• The sterility was efficiently rescued by an autosomal copy of the wild-type Chc gene reintroduced on a P element [1].
• Together, these results support a model in which HIV-1 Nef downregulates CD4 by promoting its accelerated endocytosis by a clathrin/AP2 pathway [2].

High impact information on Chc

• The only genetic evidence for kiss-and-run at the synapse comes from mutations in the genes encoding synaptojanin and endophilin, proteins that together function to uncoat vesicles in classical clathrin-mediated endocytosis [3].
• Endophilin mutations block clathrin-mediated endocytosis but not neurotransmitter release [4].
• Rapid flow of information in the nervous system involves presynaptic vesicle recycling by clathrin-mediated endocytosis, an event triggered by the alpha-adaptin-containing AP2 complex [5].
• Formation of invaginated pits on the plasma membrane and subsequent budding of vesicles is an energetically demanding process that involves the cooperation of clathrin with many different proteins [6].
• In oocytes, the major substrate for clathrin-dependent endocytosis is the vitellogenin receptor Yolkless [7].

Biological context of Chc

• The liquid facets locus encodes epsin, a vertebrate protein associated with the clathrin endocytosis complex [8].
• Mutant alleles of clathrin heavy chain, Rala, split ends, and auxilin were identified as enhancers [9].
• This DNA complemented a group of EMS-induced lethal mutations mapping to the same region of the X chromosome, thus identifying the Chc complementation group [1].
• A 13-kb genomic Drosophila fragment including the Chc transcription unit was reintroduced into the Drosophila genome via P element-mediated germline transformation [1].
• As a genetic approach to understanding the role of clathrin in cellular morphogenesis and developmental signal transduction, a clathrin heavy chain (Chc) gene of Drosophila melanogaster has been identified by a combination of molecular and classical genetic approaches [1].

Anatomical context of Chc

• Imaging Clathrin Dynamics in Drosophila melanogaster Hemocytes Reveals a Role for Actin in Vesicle Fission [10].
• In shibire(ts1), a dynamin mutant, flunarizine or La(3+) inhibited assembly of clathrin at the plasma membrane during stimulation without affecting dynamin function [11].
• A stable HeLa cell line expressing a dynamin mutant, dynts, exhibits a temperature-sensitive defect in endocytic clathrin-coated vesicle formation [12].
• Monoclonal antibodies to plant clathrin HC confirmed that coated vesicles are relatively abundant in tip-growing pollen tubes of Lilium longiflorum [13].
• Amphiphysins, members of the BAR (Bin-Amphiphysin-Rvsp) protein super family, have been postulated to play a key role in clathrin-mediated endocytosis of synaptic vesicles (SVs) [14].

Associations of Chc with chemical compounds

• This polylysine motif binds clathrin-adapter protein AP-2, neuronal calcium channels, and inositol high polyphosphates [15].
• Clathrin-coated vesicles were isolated from soybean (Glycine max L.) cells in suspension culture and their purity was assessed using SDS-PAGE, peptide sequencing and electron microscopy [13].
• These observations resemble the effect of endocytosis arrest by GTP-gamma-S in rat brain synaptosomes (Takei et al., 1995), in which dynamin is trapped at the neck of invaginated pits but is absent in the clathrin-coated distal end undergoing internalization [16].

Other interactions of Chc

• Genetic interaction studies suggest a link between the Dpp receptors and clathrin [17].
• Epsin consists of an epsin NH(2)-terminal homology (ENTH) domain that promotes the interaction with phospholipids, several AP2 binding sites, two clathrin binding sequences, and several Eps15 homology (EH) domain binding motifs [18].
• Mutations in Drosophila that delete the C2B domain of synaptotagmin disrupt clathrin AP-2 binding and endocytosis [19].
• Dynamin is a GTPase protein that is essential for clathrin-mediated endocytosis of synaptic vesicle membranes [20].
• In addition, we identified mutations in Bag, the gene encoding clathrin heavy chain and a dominant mutation of the cytosolic 70 kDa heatshock cognate protein encoded by the hsc4 gene, as Notch signaling modifier [21].

Analytical, diagnostic and therapeutic context of Chc

• Hybridization in situ to larval polytene chromosomes revealed a single Chc locus at position 13F2 on the X chromosome [1].
• Using degenerate primers based on mammalian and yeast clathrin HC sequences, a small fragment of the HC gene was amplified from genomic Drosophila DNA by the polymerase chain reaction [1].
• Immunofluorescence analysis of pollen tubes revealed that clathrin localises to the plasma membrane at the apex of the pollen tube tip, which is consistent with high levels of clathrin-mediated membrane recycling [13].

References