Cheadle, L., Biederer, T. (December 2012) The novel synaptogenic protein Farp1 links postsynaptic cytoskeletal dynamics and transsynaptic organization. J Cell Biol, 199 (6). pp. 985-1001. ISSN 0021-9525 (Print)0021-9525
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.
| Item Type: | Paper |
|---|---|
| CSHL Authors: | |
| Communities: | CSHL labs > Cheadle lab |
| Depositing User: | Matthew Dunn |
| Date: | 10 December 2012 |
| Date Deposited: | 07 Aug 2020 19:27 |
| Last Modified: | 07 Aug 2020 19:27 |
| PMCID: | PMC3518221 |
| URI: | https://repository.cshl.edu/id/eprint/39591 |
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