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Molecular and Cellular Biology, December 2002, p. 8332-8341, Vol. 22, No. 23
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.23.8332-8341.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Transport of Fragile X Mental Retardation Protein via Granules in Neurites of PC12 Cells

Yolanda De Diego Otero,1,{dagger} Lies-Anne Severijnen,1 Gert van Cappellen,2 Mariëtte Schrier,1 Ben Oostra,1 and Rob Willemsen1*

CBG Department of Clinical Genetics,1 Department of Endocrinology and Reproduction, Erasmus University, Rotterdam, The Netherlands2

Received 7 June 2002/ Returned for modification 14 August 2002/ Accepted 5 September 2002

Lack of fragile X mental retardation protein (FMRP) causes fragile X syndrome, a common form of inherited mental retardation. FMRP is an RNA binding protein thought to be involved in translation efficiency and/or trafficking of certain mRNAs. Recently, a subset of mRNAs to which FMRP binds with high affinity has been identified. These FMRP-associated mRNAs contain an intramolecular G-quartet structure. In neurons, dendritic mRNAs are involved in local synthesis of proteins in response to synaptic activity, and this represents a mechanism for synaptic plasticity. To determine the role of FMRP in dendritic mRNA transport, we have generated a stably FMR1-enhanced green fluorescent protein (EGFP)-transfected PC12 cell line with an inducible expression system (Tet-On) for regulated expression of the FMRP-GFP fusion protein. After doxycycline induction, FMRP-GFP was localized in granules in the neurites of PC12 cells. By using time-lapse microscopy, the trafficking of FMRP-GFP granules into the neurites of living PC12 cells was demonstrated. Motile FMRP-GFP granules displayed two types of movements: oscillatory (bidirectional) and unidirectional anterograde. The average velocity of the granules was 0.19 µm/s with a maximum speed of 0.71 µm/s. In addition, we showed that the movement of FMRP-GFP labeled granules into the neurites was microtubule dependent. Colocalization studies further showed that the FMRP-GFP labeled granules also contained RNA, ribosomal subunits, kinesin heavy chain, and FXR1P molecules. This report is the first example of trafficking of RNA-containing granules with FMRP as a core constituent in living PC12 cells.

* Corresponding author. Mailing address: Department of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Phone: (31) 10-4087152. Fax: (31) 10-4089489. E-mail: willemsen{at}ch1.fgg.eur.nl.

{dagger} Present address: Carlos Haya Hospital Research Laboratory, Malaga, Spain.

Molecular and Cellular Biology, December 2002, p. 8332-8341, Vol. 22, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.23.8332-8341.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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