DCX in PC12 cells: CREB-mediated transcription and neurite outgrowth

Orit Shmueli, Amos Gdalyahu, Ksenia Sorokina, Eviater Nevo, Aaron Avivi, Orly Reiner

Research output: Contribution to journalArticlepeer-review

Abstract

Mutations in doublecortin (DCX) result in X-linked lissencephaly in males. To explore the role of DCX in differentiation and signal transduction we over-expressed DCX in PC12 cells. Our results indicate that DCX stabilizes microtubules and inhibits neurite outgrowth in nerve growth factor-induced differentiation. However, neurite length is increased when differentiation is induced by epidermal growth factor and forskolin or by dibutyryl-cAMP. Furthermore, CREB-mediated transcription is downregulated, supporting the notion that cytoskeletal regulatory proteins can affect the transcriptional state of a cell. Using different constructs and mutations we reach the conclusion that microtubule stabilization is a key factor, but not the only one, in controlling neurite extension. Overexpression of a mutation found in a lissencephaly patient (S47R), completely blocks neurite outgrowth. We propose that these functions are important during normal and abnormal brain development.

Original languageEnglish
Pages (from-to)1061-1070
Number of pages10
JournalHuman Molecular Genetics
Volume10
Issue number10
DOIs
StatePublished - 1 May 2001

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Molecular Biology

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