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MBC in Press, published online ahead of print February 20, 2008
Mol. Biol. Cell 10.1091/mbc.E07-08-0802

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Submitted on August 19, 2007
Revised on January 29, 2008
Accepted on February 7, 2008

Paralemmin-1, a Modulator of Filopodia Induction is Required for Spine Maturation

Pamela Arstikaitis,* Catherine Gauthier-Campbell,* Rosario Carolina Gutierrez Herrera,{dagger} Kun Huang,* Joshua N. Levinson,* Timothy H. Murphy,* Manfred W. Kilimann,{ddagger} Carlo Sala,{sect} Michael A. Colicos,{dagger} and Alaa El-Husseini*

*Department of Psychiatry and the Brain Research Centre, University of British Columbia, Vancouver, V6T 1Z3, Canada; {sect}Department of Pharmacology, CNR Institute of Neuroscience, University of Milan, Milan, Italy; {dagger}Department of Physiology and Biophysics, Hotchkiss Brain Institute, University of Calgary, Calgary, T2N 4N1, Canada; {ddagger}Department of Cell and Molecular Biology, Uppsala University, 75124 Uppsala, Sweden

Monitoring Editor: Paul Forscher

Dendritic filopodia are thought to participate in neuronal contact formation and development of dendritic spines, however molecules that regulate filopodia extension and their maturation to spines remain largely unknown. Here we identify paralemmin-1 as a regulator of filopodia induction and spine maturation. Paralemmin-1 localizes to dendritic membranes and its ability to induce filopodia and recruit synaptic elements to contact sites requires protein acylation. Effects of paralemmin-1 on synapse maturation are modulated by alternative splicing which regulate spine formation and recruitment of AMPA-type glutamate receptors. Paralemmin-1 enrichment at the plasma membrane is subject to rapid changes in neuronal excitability and this process controls neuronal activity-driven effects on protrusion expansion. Knockdown of paralemmin-1 in developing neurons reduces the number of filopodia and spines formed and diminishes the effects of Shank1b on the transformation of existing filopodia into spines. Our study identifies a key role for paralemmin-1 in spine maturation through modulation of filopodia induction.

Address correspondence to: Pamela Arstikaitis (parstika{at}interchange.ubc.ca)






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