Abstract
Dendritic arbor architecture profoundly impacts neuronal connectivity and function, and aberrant dendritic morphology characterizes neuropsychiatric disorders. Here, we identify the adhesion-GPCR BAI1 as an important regulator of dendritic arborization. BAI1 loss from mouse or rat hippocampal neurons causes dendritic hypertrophy, whereas BAI1 overexpression precipitates dendrite retraction. These defects specifically manifest as dendrites transition from growth to stability. BAI1-mediated growth arrest is independent of its Rac1-dependent synaptogenic function. Instead, BAI1 couples to the small GTPase RhoA, driving late RhoA activation in dendrites coincident with growth arrest. BAI1 loss lowers RhoA activation and uncouples it from dendrite dynamics, causing overgrowth. None of BAI1's known downstream effectors mediates BAI1-dependent growth arrest. Rather, BAI1 associates with the Rho-GTPase regulatory protein Bcr late in development and stimulates its cryptic RhoA-GEF activity, which functions together with its Rac1-GAP activity to terminate arborization. Our results reveal a late-acting signaling pathway mediating a key transition in dendrite development.
Highlights
A dizzying array of dendritic arbors receives and processes information transiting the brain (Harris and Spacek, 2016; Landgraf and Evers, 2005; Lefebvre et al, 2015; Polavaram et al, 2014)
While no known modes of BAI1 signaling account for its ability to restrict dendritic growth, we show that it activates the small GTPase RhoA by stimulating the cryptic RhoAguanine nucleotide exchange factor (GEF) activity of the breakpoint cluster region protein (Bcr), and that Bcr’s activation of RhoA is required in concert with its inhibition of the small GTPase Rac1 to mediate growth arrest
We identified a new mechanism for restricting dendrite growth that connects the A-GPCR BAI1 to the small GTPase RhoA through Bcr
Summary
A dizzying array of dendritic arbors receives and processes information transiting the brain (Harris and Spacek, 2016; Landgraf and Evers, 2005; Lefebvre et al, 2015; Polavaram et al, 2014). Arbor morphology controls neuronal availability to inputs (Landgraf and Evers, 2005; Lefebvre et al, 2015; Hausser and Mel, 2003) and contributes to input processing (Hausser and Mel, 2003; Grienberger et al, 2015; Henze et al, 1996; London and Hausser, 2005).
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