Paralemmin-1, a modulator of filopodia induction is required for spine maturation

Mol Biol Cell. 2008 May;19(5):2026-38. doi: 10.1091/mbc.e07-08-0802. Epub 2008 Feb 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Animals
  • COS Cells
  • Cell Membrane / metabolism
  • Chlorocebus aethiops
  • Dendritic Spines / metabolism*
  • Lipoylation
  • Membrane Proteins / metabolism*
  • Mice
  • Phosphoproteins / metabolism*
  • Protein Transport
  • Pseudopodia / metabolism*
  • Rats
  • Receptors, AMPA / metabolism
  • Time Factors

Substances

  • Membrane Proteins
  • Palm protein, rat
  • Phosphoproteins
  • Receptors, AMPA
  • glutamate receptor ionotropic, AMPA 1