Dendritic trafficking of BDNF mRNA is mediated by translin and blocked by the G196A (Val66Met) mutation

C. Chiaruttini, A. Vicario, Z. Li, G. Baj, P. Braiuca, Y. Wu, F. S. Lee, L. Gardossi, J. M. Baraban, E. Tongiorgi

Research output: Contribution to journalArticlepeer-review

Abstract

Alternatively spliced brain-derived neurotrophic factor (BDNF) transcripts are targeted to distinct cellular compartments in neurons but the mechanisms underlying this sorting are unknown. Although only some BDNF isoforms are targeted to dendrites, we have found that the coding region common to all BDNF transcripts contains a constitutively active dendritic targeting signal and that this signal is suppressed in transcripts containing exons 1 or 4, which are restricted to the cell soma and proximal dendrites. This dendritic targeting signal is mediated by translin, an RNA-binding protein implicated in RNA trafficking, and is disrupted by the G196A mutation associated with memory deficits and psychiatric disorders. Molecular modeling and mutational studies indicate that the G196A mutation blocks dendritic targeting of BDNF mRNA by disrupting its interaction with translin. These findings implicate abnormal dendritic trafficking of BDNF mRNA in the pathophysiology of neuropsychiatric disorders linked to the G196A mutation.

Original languageEnglish (US)
Pages (from-to)16481-16486
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number38
DOIs
StatePublished - Sep 22 2009

Keywords

  • Neuropsychiatric disorders
  • Neurotrophins

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Dendritic trafficking of BDNF mRNA is mediated by translin and blocked by the G196A (Val66Met) mutation'. Together they form a unique fingerprint.

Cite this