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PMID:19027066

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Citation

Peralta, S, Gómez, Y, González-Gaitán, MA, Moya, F and Vinós, J Notch down-regulation by endocytosis is essential for pigment cell determination and survival in the Drosophila retina. Mech. Dev. 126:256-69

Abstract

The clathrin heavy chain is a fundamental element in endocytosis and therefore, in the internalization of several cell-surface receptors through which cells interact with their environment. Here we show that the only non-lethal mutant allele of the clathrin heavy chain identified to date in metazoans, the Drosophila Chc(4), involves the substitution of a residue at the knee region of the molecule that impairs clathrin-dependent endocytosis. We have investigated the consequences of this endocytic defect in Drosophila retinal development and found that it produces an inhibition of programmed cell death in the retinal lattice, followed by widespread death of interommatidial pigment cells once retinal development has been completed. Through genetic interactions and transgenic analyses, we show that Chc(4) phenotypes are caused by a Notch receptor gain-of-function, providing a dramatic example of the importance of Notch down-regulation by endocytosis. An increase in Notch signaling is also observed in Drosophila wings in response to the mutant clathrin, suggesting that Notch levels are controlled by clathrin-dependent endocytosis. We discuss the implications of these findings for current models on eye-development and for the role of endocytosis in Notch signaling.

Links

PubMed Online version:10.1016/j.mod.2008.10.011

Keywords

Amino Acid Sequence; Amino Acid Substitution; Animals; Apoptosis; Cell Lineage; Cell Survival; Clathrin Heavy Chains/genetics; Down-Regulation; Drosophila melanogaster/cytology; Drosophila melanogaster/metabolism; Drosophila melanogaster/ultrastructure; Endocytosis; Models, Biological; Molecular Sequence Data; Mutation/genetics; Phenotype; Photoreceptor Cells, Invertebrate/cytology; Photoreceptor Cells, Invertebrate/metabolism; Photoreceptor Cells, Invertebrate/ultrastructure; Protein Transport; Pupa/cytology; Receptors, Notch/chemistry; Receptors, Notch/metabolism; Retina/cytology; Retina/metabolism; Retina/ultrastructure; Subcellular Fractions/metabolism; Wing/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:NOTCH

involved_in

GO:0008587: imaginal disc-derived wing margin morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:DYN

involved_in

GO:0046667: compound eye retinal cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:CLH

involved_in

GO:0046667: compound eye retinal cell programmed cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:CLH

involved_in

GO:0045807: positive regulation of endocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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