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Originally published as MBC in Press, 10.1091/mbc.E07-08-0802 on February 20, 2008

Vol. 19, Issue 5, 2026-2038, May 2008

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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§, Michael A. Colicos{dagger}, and Alaa El-Husseini*

*Department of Psychiatry and the Brain Research Centre, University of British Columbia, Vancouver, V6T 1Z3, Canada; §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; and {ddagger}Department of Cell and Molecular Biology, Uppsala University, 75124 Uppsala, Sweden

Submitted August 19, 2007; Revised January 29, 2008; Accepted February 7, 2008
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 that regulates 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.


This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-08-0802) on February 20, 2008.

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







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