The expression of the PDZ protein MALS-1/velis is regulated by calcium and calcineurin in cerebellar granule cells.
Activity-dependent gene expression is thought to be important in shaping neuronal development and in modifying the protein content of neurons. Ca(2+) entry into neurons appears to be one of the key effectors of activity-dependent gene expression. Among the possible downstream targets of calcium, the protein phosphatase calcineurin represents a prime candidate. We hereby report that in cultured cerebellar granule cells the activation of the Ca(2+)/calcineurin pathway via either voltage- or ligand- operated Ca(2+) channels regulates MALS-1 and MALS-2 expression at the transcriptional level. These proteins are integral parts of the post-synaptic density and are also involved in receptor trafficking. MALS regulation is not at the level of mRNA stability and does not require de novo protein synthesis, thereby suggesting a direct pathway. These data suggest that Ca(2+) entry by means of calcineurin is capable of controlling the structure of the post-synaptic density by controlling the expression of key components at the transcriptional level.
Sanna
Bastiano
B
Department of Pharmacology, Tennis Court Road, Cambridge CB2 1PD, United Kingdom.
Kramer
Dana
D
Genazzani
Armando A
AA
D000818:Animals; D015153:Blotting, Western; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D008024:Ligands; D008565:Membrane Proteins; D009474:Neurons / Q000378:metabolism; D014176:Protein Biosynthesis; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses; D013997:Time Factors; D014158:Transcription, Genetic; D015854:Up-Regulation; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D008024:Ligands; C114670:Lin7a protein, mouse; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; D019703:Calcineurin; D002118:Calcium