New insights into the molecular basis of progressive myoclonus epilepsy: a multiprotein complex with cystatin B.
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.
Di Giaimo
Rossella
R
Department of Biology, Bologna University, 40126 Bologna, Italy.
Riccio
Massimo
M
Santi
Spartaco
S
Galeotti
Cesira
C
Ambrosetti
Davide C
DC
Melli
Marialuisa
M
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
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