Presence and phosphorylation of transcription factors in developing denotes

P. Crino, Kamran Khodakhah, K. Becker, S. Ginsberg, S. Hemby, J. Eberwine

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

In screening amplified poly(A) mRNA from hippocampal dendrites and growth in culture to determine candidates for local translation, we found that select transcription factor mRNAs were present. We hypothesized that synthesis of transcription factor proteins within dendrites would provide a direct signaling pathway between the distal dendrite and the nucleus resulting in modulation of gene expression important for neuronal differentiation. To evaluate this possibility, radiolabeled amplified antisense RNA was used to probe slot blots of transcription factor cDNAs as well as arrayed blots of zinc finger transcription factors. The mRNAs encoding the cAMP response element binding protein (CREB), zif 268, and one putative transcription factor were detected. We expanded upon these results showing that CREB protein is present in dendrites, that translation of CREB mRNA in isolated dendrites is feasible and that CREB protein found in dendrites can interact with the cis-acting cyclic AMP reponse element DNA sequence by using an in situ Southwestern assay. Further, CREB protein in dendrites is not transported to this site from the cell body because fluorescently tagged CREB microperfused into the soma did not diffuse into the dendrites. In addition, CREB protein microperfused into dendrites was rapidly transported to the nucleus, its likely site of bioactivity. Lastly, by using the isolated dendrite system we show that phosphorylation of Ser- 133 on CREB protein can occur in isolated dendrites independent of the nucleus. These data provide a regulatory pathway in which transcription factors synthesized posttranslationally modified in dendrites directly alter gene expression bypassing the integration of signal transduction pathways that converge on the nucleus.

Original languageEnglish (US)
Pages (from-to)2313-2318
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number5
DOIs
StatePublished - Mar 3 1998
Externally publishedYes

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Dendrites
Cyclic AMP Response Element-Binding Protein
Transcription Factors
Phosphorylation
Messenger RNA
Proteins
Gene Expression
Antisense RNA
Zinc Fingers
Carisoprodol
Cyclic AMP
Signal Transduction
Complementary DNA

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Presence and phosphorylation of transcription factors in developing denotes. / Crino, P.; Khodakhah, Kamran; Becker, K.; Ginsberg, S.; Hemby, S.; Eberwine, J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 5, 03.03.1998, p. 2313-2318.

Research output: Contribution to journalArticle

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