The γ-Protocadherins Interact Physically and Functionally with Neuroligin-2 to Negatively Regulate Inhibitory Synapse Density and Are Required for Normal Social Interaction

Development of FRET-based indicators for visualizing homophilic trans interaction of a clustered protocadherin

“…Notably, a single Pcdh isoform was able to rescue these abnormalities in retinal SAC cells 11,12 . In addition, Pcdh has been observed to be involved in a wide range of biological phenomena, such as axonal coalescence of olfactory sensory neurons 14,15 , axonal projection of serotonergic neurons [16][17][18] , formation of dendrite branching complexity [19][20][21] , and synapse maturation 22,23 .Till date, Pcdh interaction analysis has relied primarily on cell aggregation assays using K562 cells 6,7,24-28 . Because K562 cells lack endogenous cell adhesion molecules and they are observed as separate cells under a microscope, the binding property of the cell adhesion molecules introduced into K562 cells can be evaluated as cell aggregates 29 .…”

“…Notably, a single Pcdh isoform was able to rescue these abnormalities in retinal SAC cells 11,12 . In addition, Pcdh has been observed to be involved in a wide range of biological phenomena, such as axonal coalescence of olfactory sensory neurons 14,15 , axonal projection of serotonergic neurons [16][17][18] , formation of dendrite branching complexity [19][20][21] , and synapse maturation 22,23 .…”

Collective Mechanical Responses of Cadherin-Based Adhesive Junctions as Predicted by Simulations

“…While simulated timescales are short (hundreds of nanoseconds), the simulated conditions used are equivalent to those experienced by tissues exposed to blunt trauma (126,127), and we expect that our quantitative predictions from stretching simulations at fast speeds will provide upper bounds for elasticity and unbinding forces, with qualitative predictions holding even at near equilibrium conditions (103,104,110,(156)(157)(158). Future modeling efforts should focus on taking into account the effect of Ca 2+ , glycosylation, membrane, and cytoplasmic partners on the tensile and shearing mechanics of junctions that might not only include mixtures of cadherin proteins, such as classical and clustered or delta-protocadherins (159)(160)(161), but also complexes with neuroligins, nectins, and other proteins partners (97,(162)(163)(164)(165).…”

“…However, axon growth and neuronal circuit formation during brain development is a dynamic process in which mechanical forces play a role (66), and forcegenerating and load-bearing proteins are also thought to regulate synapse development and function (67)(68)(69), while action potentials can cause neuronal deformation (70)(71)(72)(73)(74)(75), and traumatic brain injury can disrupt neuronal adhesion (76). Interestingly, the clustered protocadherin (PCDH) proteins, a subtype of cadherins expressed predominantly in the nervous system (77)(78)(79)(80)(81)(82)(83), form adhesive junctions (84)(85)(86)(87)(88)(89)(90) thought to signal for self-avoidance (91)(92)(93) and that may also be involved in synapse maturation and function (94)(95)(96)(97)(98). The clustered PCDH junctions may need to withstand mechanical stimuli, albeit in a different cellular and functional context than classical cadherins.…”

Development of FRET-Based Indicators For Visualizing Homophilic Trans Interaction of A Clustered Protocadherin

“…Notably, a single Pcdh isoform was able to rescue these abnormalities in retinal SAC cells [11,12] . In addition, Pcdh has been observed to be involved in a wide range of biological phenomena, such as axonal coalescence of olfactory sensory neurons [14,15] , axonal projection of serotonergic neurons [16][17][18] , formation of dendrite branching complexity [19][20][21] , and synapse maturation [22,23] . Till date, Pcdh interaction analysis has relied primarily on cell aggregation assays using K562 cells [6,7,[24][25][26][27][28] .…”