title: Paralemmin-1, a modulator of filopodia induction is required for spine maturation.
abstract: 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.
authors.affiliation: Department of Psychiatry and the Brain Research Centre, University of British Columbia, Vancouver, V6T 1Z3, Canada. parstika@interchange.ubc.ca
authors.forename: Pamela
authors.initials: P
authors.lastname: Arstikaitis
authors.forename: Catherine
authors.initials: C
authors.lastname: Gauthier-Campbell
authors.forename: Rosario
authors.initials: R
authors.lastname: Carolina Gutierrez Herrera
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Levinson
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Murphy
authors.forename: Manfred W
authors.initials: MW
authors.lastname: Kilimann
authors.forename: Carlo
authors.initials: C
authors.lastname: Sala
authors.forename: Michael A
authors.initials: MA
authors.lastname: Colicos
authors.forename: Alaa
authors.initials: A
authors.lastname: El-Husseini
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000378:metabolism*; D054878:Lipoylation; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D021381:Protein Transport; D011554:Pseudopodia / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D013997:Time Factors
chemical_list: D008565:Membrane Proteins; D010750:Phosphoproteins; D018091:Receptors, AMPA; C523858:Palm protein, rat