Abstract
The delta-protocadherins (δ-Pcdhs) play key roles in neural development, and expression studies suggest they are expressed in combination within neurons. The extent of this combinatorial diversity, and how these combinations influence cell adhesion, is poorly understood. We show that individual mouse olfactory sensory neurons express 0-7 δ-Pcdhs. Despite this apparent combinatorial complexity, K562 cell aggregation assays revealed simple principles that mediate tuning of δ-Pcdh adhesion. Cells can vary the number of δ-Pcdhs expressed, the level of surface expression, and which δ-Pcdhs are expressed, as different members possess distinct apparent adhesive affinities. These principles contrast with those identified previously for the clustered protocadherins (cPcdhs), where the particular combination of cPcdhs expressed does not appear to be a critical factor. Despite these differences, we show δ-Pcdhs can modify cPcdh adhesion. Our studies show how intra- and interfamily interactions can greatly amplify the impact of this small subfamily on neuronal function.
Highlights
The delta-protocadherins (d-Pcdhs) are a nine-member subfamily of the cadherin superfamily (Hulpiau and van Roy, 2009; Nollet et al, 2000), and play diverse roles during neural development
Our results argue that differences in apparent adhesive affinity and relative surface expression regulate coaggregation behavior
Our results provide a foundation for understanding how a small gene family can exert unexpectedly complex influences on cell adhesion
Summary
The delta-protocadherins (d-Pcdhs) are a nine-member subfamily of the cadherin superfamily (Hulpiau and van Roy, 2009; Nollet et al, 2000), and play diverse roles during neural development. Mutations in PCDH19 are the causative basis of one form of epilepsy (Dibbens et al, 2008), and other d-Pcdhs are implicated in various neurological disorders (Chang et al, 2018; Consortium on Complex Epilepsies, 2014; Morrow et al, 2008) How does this relatively small gene family mediate these varied effects? Double label RNA in situ hybridization studies indicate individual neurons express more than one dPcdh (Etzrodt et al, 2009; Krishna-K et al, 2011). This suggests a model where different combinations of d-Pcdhs may be expressed within different populations of neurons. To postulate that combinatorial expression would greatly enhance the impact
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