Calcineurin controls the expression of numerous genes in cerebellar granule cells.
The Ca(2+)/calmodulin-dependent phosphatase calcineurin plays a crucial role in gene expression in different cell types such as T-lymphocytes, cardiac myocytes, and smooth muscle cells. A possible role for calcineurin in gene expression was recently found in neurons, where calcineurin regulates the expression of several genes involved in Ca(2+) homeostasis. To detect additional genes regulated in a calcineurin-dependent way in neurons we analysed gene expression profiles of cerebellar granule cells cultured in depolarising conditions in the presence or absence of the calcineurin inhibitory agents FK506 and CsA. Using oligonucleotide arrays we identified 34 genes that are differentially expressed between the samples and confirmed the calcineurin-dependent regulation of some of these genes by RT-PCR. Therefore, our results, which are likely not to be comprehensive, suggest that calcineurin plays a fundamental role in neuronal gene expression by either activating or repressing the expression of genes such as receptors, transcription factors, and signalling molecules.
Kramer
Dana
D
Department of Pharmacology, Tennis Court Road, Cambridge, CB2 1PD, UK.
Fresu
Luigia
L
Ashby
Dominique S
DS
Freeman
Tom C
TC
Genazzani
Armando A
AA
D000818:Animals; D000831:Animals, Newborn; D019703:Calcineurin / Q000235:genetics* / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D020013:Calcium Signaling / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D016559:Tacrolimus / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D065095:Calcineurin Inhibitors; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D019703:Calcineurin; D016559:Tacrolimus