title: γ-Protocadherins Interact with Neuroligin-1 and Negatively Regulate Dendritic Spine Morphogenesis.
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.
authors.affiliation: Graduate Program in Genetics, The University of Iowa, Iowa City, IA 52242, USA; Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Molumby
authors.affiliation: Department of Psychological and Brain Sciences, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Anderson
authors.affiliation: Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Dillan J
authors.initials: DJ
authors.lastname: Newbold
authors.affiliation: Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Norah K
authors.initials: NK
authors.lastname: Koblesky
authors.affiliation: Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Garrett
authors.affiliation: Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schreiner
authors.affiliation: Department of Psychological and Brain Sciences, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Radley
authors.affiliation: Graduate Program in Genetics, The University of Iowa, Iowa City, IA 52242, USA; Department of Biology, The University of Iowa, Iowa City, IA 52242, USA; Department of Psychiatry, The University of Iowa, Iowa City, IA 52242, USA. Electronic address: joshua-weiner@uiowa.edu.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Weiner
mesh_terms: D000818:Animals; D019556:COS Cells; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis; D017729:Presynaptic Terminals / Q000378:metabolism; D011485:Protein Binding
chemical_list: D000070585:Cadherin Related Proteins; D015820:Cadherins; D015816:Cell Adhesion Molecules, Neuronal; C464785:Gamma-protocadherins; D009419:Nerve Tissue Proteins; C093438:neuroligin 1; C086959:neurexin Ibeta
keywords: Pcdh; Protocadherin; Protocadherins; cell adhesion; neurexin; spine maturation; spine morphology; synapse formation; synapse maturation; synaptogenesis