RGD Reference Report - Calpain hydrolysis of alpha- and beta2-adaptins decreases clathrin-dependent endocytosis and may promote neurodegeneration. - Rat Genome Database
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Calpain hydrolysis of alpha- and beta2-adaptins decreases clathrin-dependent endocytosis and may promote neurodegeneration.

Authors: Rudinskiy, Nikita  Grishchuk, Yulia  Vaslin, Anne  Puyal, Julien  Delacourte, AndrĂ©  Hirling, Harald  Clarke, Peter G H  Luthi-Carter, Ruth 
Citation: Rudinskiy N, etal., J Biol Chem. 2009 May 1;284(18):12447-58. doi: 10.1074/jbc.M804740200. Epub 2009 Feb 24.
RGD ID: 13461853
Pubmed: (View Article at PubMed) PMID:19240038
DOI: Full-text: DOI:10.1074/jbc.M804740200

Clathrin-dependent endocytosis is mediated by a tightly regulated network of molecular interactions that provides essential protein-protein and protein-lipid binding activities. Here we report the hydrolysis of the alpha- and beta2-subunits of the tetrameric adaptor protein complex 2 by calpain. Calcium-dependent alpha- and beta2-adaptin hydrolysis was observed in several rat tissues, including brain and primary neuronal cultures. Neuronal alpha- and beta2-adaptin cleavage was inducible by glutamate stimulation and was accompanied by the decreased endocytosis of transferrin. Heterologous expression of truncated forms of the beta2-adaptin subunit significantly decreased the membrane recruitment of clathrin and inhibited clathrin-mediated receptor endocytosis. Moreover, the presence of truncated beta2-adaptin sensitized neurons to glutamate receptor-mediated excitotoxicity. Proteolysis of alpha- and beta2-adaptins, as well as the accessory clathrin adaptors epsin 1, adaptor protein 180, and the clathrin assembly lymphoid myeloid leukemia protein, was detected in brain tissues after experimentally induced ischemia and in cases of human Alzheimer disease. The present study further clarifies the central role of calpain in regulating clathrin-dependent endocytosis and provides evidence for a novel mechanism through which calpain activation may promote neurodegeneration: the sensitization of cells to glutamate-mediated excitotoxicity via the decreased internalization of surface receptors.

Annotation

Disease Annotations    

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Ap2b1  (adaptor related protein complex 2 subunit beta 1)
Epn1  (Epsin 1)
Snap91  (synaptosome associated protein 91)

Genes (Mus musculus)
Ap2b1  (adaptor-related protein complex 2, beta 1 subunit)
Epn1  (epsin 1)
Snap91  (synaptosomal-associated protein 91)

Genes (Homo sapiens)
AP2B1  (adaptor related protein complex 2 subunit beta 1)
EPN1  (epsin 1)
SNAP91  (synaptosome associated protein 91)


Additional Information