The novel synaptogenic protein Farp1 links postsynaptic cytoskeletal dynamics and transsynaptic organization
Open Access
- 3 December 2012
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 199 (6), 985-1001
- https://doi.org/10.1083/jcb.201205041
Abstract
Synaptic adhesion organizes synapses, yet the signaling pathways that drive and integrate synapse development remain incompletely understood. We screened for regulators of these processes by proteomically analyzing synaptic membranes lacking the synaptogenic adhesion molecule SynCAM 1. This identified FERM, Rho/ArhGEF, and Pleckstrin domain protein 1 (Farp1) as strongly reduced in SynCAM 1 knockout mice. Farp1 regulates dendritic filopodial dynamics in immature neurons, indicating roles in synapse formation. Later in development, Farp1 is postsynaptic and its 4.1 protein/ezrin/radixin/moesin (FERM) domain binds SynCAM 1, assembling a synaptic complex. Farp1 increases synapse number and modulates spine morphology, and SynCAM 1 requires Farp1 for promoting spines. In turn, SynCAM 1 loss reduces the ability of Farp1 to elevate spine density. Mechanistically, Farp1 activates the GTPase Rac1 in spines downstream of SynCAM 1 clustering, and promotes F-actin assembly. Farp1 furthermore triggers a retrograde signal regulating active zone composition via SynCAM 1. These results reveal a postsynaptic signaling pathway that engages transsynaptic interactions to coordinate synapse development.Keywords
This publication has 66 references indexed in Scilit:
- Lateral assembly of the immunoglobulin protein SynCAM 1 controls its adhesive function and instructs synapse formationThe EMBO Journal, 2011
- Acute knockdown of AMPA receptors reveals a trans-synaptic signal for presynaptic maturationThe EMBO Journal, 2011
- SynCAM 1 Adhesion Dynamically Regulates Synapse Number and Impacts Plasticity and LearningNeuron, 2010
- A network of networks: cytoskeletal control of compartmentalized function within dendritic spinesCurrent Opinion in Neurobiology, 2010
- Coordinated Actions of Actin and BAR Proteins Upstream of Dynamin at Endocytic Clathrin-Coated PitsDevelopmental Cell, 2009
- FARP1 Promotes the Dendritic Growth of Spinal Motor Neuron Subtypes through Transmembrane Semaphorin6A and PlexinA4 SignalingNeuron, 2009
- EphB Receptors Couple Dendritic Filopodia Motility to Synapse FormationNeuron, 2008
- Expression and adhesion profiles of SynCAM molecules indicate distinct neuronal functionsJournal of Comparative Neurology, 2008
- Synapses between corticotropin‐releasing factor‐containing axon terminals and dopaminergic neurons in the ventral tegmental area are predominantly glutamatergicJournal of Comparative Neurology, 2007
- p120 Catenin Regulates Dendritic Spine and Synapse Development through Rho-Family GTPases and CadherinsNeuron, 2006