title: New insights into the molecular basis of progressive myoclonus epilepsy: a multiprotein complex with cystatin B.
abstract: Cystatin B is an anti-proteolytic polypeptide implicated in progressive myoclonus epilepsy (EPM1), a degenerative disease of the central nervous system. The knock-out mouse model of the disease shows apoptosis of the cerebellar granule cells. We have identified five recombinant proteins interacting with cystatin B and none of them is a protease. We show that three of these proteins (RACK-1, beta-spectrin and NF-L) co-immunoprecipitate with cystatin B in rat cerebellum. Confocal immunofluorescence analysis shows that the same proteins are present in the granule cells of developing cerebellum, as well as in Purkinje cells of adult rat cerebellum. We propose that a cystatin B multiprotein complex has a specific cerebellar function and that the loss of this function might contribute to the disease in EPM1 patients.
authors.affiliation: Department of Biology, Bologna University, 40126 Bologna, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Di Giaimo
authors.forename: Massimo
authors.initials: M
authors.lastname: Riccio
authors.forename: Spartaco
authors.initials: S
authors.lastname: Santi
authors.forename: Cesira
authors.initials: C
authors.lastname: Galeotti
authors.forename: Davide C
authors.initials: DC
authors.lastname: Ambrosetti
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Melli
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002531:Cerebellum / Q000378:metabolism*; D055313:Cystatin B; D015891:Cystatins / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D018613:Microscopy, Confocal; D046912:Multiprotein Complexes; D020191:Myoclonic Epilepsies, Progressive / Q000209:etiology / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011233:Precipitin Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins; D013049:Spectrin / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: C524994:CSTB protein, human; C524992:Cstb protein, mouse; D015891:Cystatins; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C044882:neurofilament protein L; D013049:Spectrin; D055313:Cystatin B; D005982:Glutathione Transferase