PMID: 11331616May 2, 2001Paper

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

Human Molecular Genetics
O ShmueliOrly Reiner

Abstract

Mutations in doublecortin (DCX) result in X-linked lissencephaly in males. To explore the role of DCX in differentiation and signal transduction we overexpressed 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.

Citations

Oct 31, 2002·The European Journal of Neuroscience·Barbara MontiAntonio Contestabile
Jun 1, 2005·Molecular and Cellular Biology·Kausik ChakrabartiMartin R Schiller
Dec 14, 2007·Developmental Neuroscience·Dror CohenOrly Reiner
Mar 1, 2008·BMC Biotechnology·Lihao MengBarry Schweitzer
May 1, 2007·Journal of Chemical Neuroanatomy·Emilio VareaJuan Nàcher
Jun 2, 2005·The European Journal of Neuroscience·Jun HeFulton T Crews
Jun 14, 2016·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Meng-Han TsaiJin-Wu Tsai
Jul 9, 2004·Developmental Cell·Anna Akhmanova, Fedor Severin
Feb 17, 2005·Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B·Silvestre OltraVictoria Castel

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