title: Proteins that promote filopodia stability, but not number, lead to more axonal-dendritic contacts.
abstract: Dendritic filopodia are dynamic protrusions that are thought to play an active role in synaptogenesis and serve as precursors to spine synapses. However, this hypothesis is largely based on a temporal correlation between filopodia formation and synaptogenesis. We investigated the role of filopodia in synapse formation by contrasting the roles of molecules that affect filopodia elaboration and motility, versus those that impact synapse induction and maturation. We used a filopodia inducing motif that is found in GAP-43, as a molecular tool, and found this palmitoylated motif enhanced filopodia number and motility, but reduced the probability of forming a stable axon-dendrite contact. Conversely, expression of neuroligin-1 (NLG-1), a synapse inducing cell adhesion molecule, resulted in a decrease in filopodia motility, but an increase in the number of stable axonal contacts. Moreover, RNAi knockdown of NLG-1 reduced the number of presynaptic contacts formed. Postsynaptic scaffolding proteins such as Shank1b, a protein that induces the maturation of spine synapses, increased the rate at which filopodia transformed into spines by stabilization of the initial contact with axons. Taken together, these results suggest that increased filopodia stability and not density, may be the rate-limiting step for synapse formation.
authors.affiliation: Department of Psychiatry and The Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Pamela
authors.initials: P
authors.lastname: Arstikaitis
authors.forename: Catherine
authors.initials: C
authors.lastname: Gauthier-Campbell
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.forename: Alaa
authors.initials: A
authors.lastname: El-Husseini
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Murphy
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001369:Axons / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism*; D051381:Rats; D013569:Synapses / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins