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Vol. 19, Issue 5, 2026-2038, May 2008
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*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;
Department of Physiology and Biophysics, Hotchkiss Brain Institute, University of Calgary, Calgary, T2N 4N1, Canada; and
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.
Address correspondence to: Pamela Arstikaitis (parstika{at}interchange.ubc.ca)