Journal article
γ-Protocadherins Interact with Neuroligin-1 and Negatively Regulate Dendritic Spine Morphogenesis
Cell reports (Cambridge), Vol.18(11), pp.2702-2714
03/14/2017
DOI: 10.1016/j.celrep.2017.02.060
PMCID: PMC5418859
PMID: 28297673
Abstract
The 22 γ-Protocadherin (γ-Pcdh) cell adhesion molecules are critical for the elaboration of complex dendritic arbors in the cerebral cortex. Here, we provide evidence that the γ-Pcdhs negatively regulate synapse development by inhibiting the postsynaptic cell adhesion molecule, neuroligin-1 (Nlg1). Mice lacking all γ-Pcdhs in the forebrain exhibit significantly increased dendritic spine density in vivo, while spine density is significantly decreased in mice overexpressing one of the 22 γ-Pcdh isoforms. Co-expression of γ-Pcdhs inhibits the ability of Nlg1 to increase spine density and to induce presynaptic differentiation in hippocampal neurons in vitro. The γ-Pcdhs physically interact in cis with Nlg1 both in vitro and in vivo, and we present evidence that this disrupts Nlg1 binding to its presynaptic partner neurexin1β. Together with prior work, these data identify a mechanism through which γ-Pcdhs could coordinate dendrite arbor growth and complexity with spine maturation in the developing brain.
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•γ-Protocadherins (γ-Pcdhs) regulate dendritic spine morphogenesis in the cerebral cortex•γ-Pcdhs interact with neuroligin-1 (Nlg1) and inhibit its interaction with neurexin1β•γ-Pcdhs inhibit Nlg1’s ability to induce presynaptic differentiation in vitro•γ-Pcdhs inhibit Nlg1’s ability to increase dendritic spine density in vitro
Using conditional mutant and overexpression mouse lines, Molumby et al. demonstrate that γ-Protocadherins negatively regulate cortical dendritic spine morphogenesis in vivo. The γ-Protocadherins interact physically with neuroligin-1 and inhibit its ability to bind neurexin1β, to promote presynaptic differentiation, and to increase dendritic spine density in hippocampal neurons in vitro.
Details
- Title: Subtitle
- γ-Protocadherins Interact with Neuroligin-1 and Negatively Regulate Dendritic Spine Morphogenesis
- Creators
- Michael J Molumby - Graduate Program in Genetics, The University of Iowa, Iowa City, IA 52242, USARachel M Anderson - Department of Psychological and Brain Sciences, The University of Iowa, Iowa City, IA 52242, USADillan J Newbold - Department of Biology, The University of Iowa, Iowa City, IA 52242, USANorah K Koblesky - Department of Biology, The University of Iowa, Iowa City, IA 52242, USAAndrew M Garrett - Department of Biology, The University of Iowa, Iowa City, IA 52242, USADietmar Schreiner - Department of Biology, The University of Iowa, Iowa City, IA 52242, USAJason J Radley - Department of Psychological and Brain Sciences, The University of Iowa, Iowa City, IA 52242, USAJoshua A Weiner - Graduate Program in Genetics, The University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.18(11), pp.2702-2714
- DOI
- 10.1016/j.celrep.2017.02.060
- PMID
- 28297673
- PMCID
- PMC5418859
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: NIH, award: R01 NS055272; DOI: 10.13039/100000912, name: March of Dimes, award: FY11-456; DOI: 10.13039/100012138, name: Nellie Ball Research Trust
- Language
- English
- Date published
- 03/14/2017
- Academic Unit
- Liberal Arts and Science Admin; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Biology
- Record Identifier
- 9983997437002771
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