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Dendritic mRNA targeting of Jacob and N-methyl-d-aspartate-induced nuclear translocation after calpain-mediated proteolysis.
Kindler, Stefan; Dieterich, Daniela C; Schütt, Janin; Sahin, Jale; Karpova, Anna; Mikhaylova, Marina; Schob, Claudia; Gundelfinger, Eckart D; Kreienkamp, Hans-Jürgen; Kreutz, Michael R.
Afiliação
  • Kindler S; Institute of Human Genetics, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany.
J Biol Chem ; 284(37): 25431-40, 2009 Sep 11.
Article em En | MEDLINE | ID: mdl-19608740
ABSTRACT
Jacob is a recently identified plasticity-related protein that couples N-methyl-d-aspartate receptor activity to nuclear gene expression. An expression analysis by Northern blot and in situ hybridization shows that Jacob is almost exclusively present in brain, in particular in the cortex and the limbic system. Alternative splicing gives rise to multiple mRNA variants, all of which exhibit a prominent dendritic localization in the hippocampus. Functional analysis in primary hippocampal neurons revealed that a predominant cis-acting dendritic targeting element in the 3'-untranslated region of Jacob mRNAs is responsible for dendritic mRNA localization. In the mouse brain, Jacob transcripts are associated with both the fragile X mental retardation protein, a well described trans-acting factor regulating dendritic mRNA targeting and translation, and the kinesin family member 5C motor complex, which is known to mediate dendritic mRNA transport. Jacob is susceptible to rapid protein degradation in a Ca(2+)- and Calpain-dependent manner, and Calpain-mediated clipping of the myristoylated N terminus of Jacob is required for its nuclear translocation after N-methyl-d-aspartate receptor activation. Our data suggest that local synthesis in dendrites may be necessary to replenish dendritic Jacob pools after truncation of the N-terminal membrane anchor and concomitant translocation of Jacob to the nucleus.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Calpaína / Receptores de N-Metil-D-Aspartato / Transporte Ativo do Núcleo Celular / Dendritos / Proteínas do Tecido Nervoso Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2009 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Calpaína / Receptores de N-Metil-D-Aspartato / Transporte Ativo do Núcleo Celular / Dendritos / Proteínas do Tecido Nervoso Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2009 Tipo de documento: Article