The adhesion-GPCR BAI1 shapes dendritic arbors via Bcr-mediated RhoA activation causing late growth arrest

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 neuron...

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Bibliographic Details
Published in:eLife 2019-08, Vol.8
Main Authors: Duman, Joseph G, Mulherkar, Shalaka, Tu, Yen-Kuei, Erikson, Kelly C, Tzeng, Christopher P, Mavratsas, Vasilis C, Ho, Tammy Szu-Yu, Tolias, Kimberley F
Format: Article
Language:English
Subjects:
Angiogenic Proteins - metabolism
Animals
branching
Cell Proliferation
Cells, Cultured
Dendrites - metabolism
Developmental Biology
hippocampal cultures
Long-Evans rats
Mice
Neuroscience
Proto-Oncogene Proteins c-bcr - metabolism
Raichu
Rats
retraction
rhoA GTP-Binding Protein - metabolism
RhoA-FLARE
Signal Transduction
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.47566