TY - JOUR
T1 - The adhesion-GPCR BAI1 shapes dendritic arbors via bcr-mediated rhoa activation causing late growth arrest
AU - Duman, Joseph G.
AU - Mulherkar, Shalaka
AU - Tu, Yen Kuei
AU - Erikson, Kelly C.
AU - Tzeng, Christopher P.
AU - Mavratsas, Vasilis C.
AU - Szu-Yu Ho, Tammy
AU - Tolias, Kimberley F.
N1 - Funding Information:
We thank M Matsuda (University of Kyoto), K Hahn (University of North Carolina), Y Nakamura (University of Tokyo), K Ravichandran (University of Virginia), and M Rasband (Baylor College of Medicine) for providing DNA constructs. We also thank N Heisterkamp (Children's Hospital Los Angeles) for creating and sharing the Bcr KO mice. We also thank M Taylor, K Firozi, T Munjal, K Um, and B Schwechter for technical assistance. This work was supported by National Institute of Neurological Disorders and Stroke grant R01NS062829 (KFT), National Institute of Mental Health grants R01MH109511 (KFT) and K01MH089112 (JGD), and the Mission Connect-TIRR Foundation (KFT).
Funding Information:
We thank M Matsuda (University of Kyoto), K Hahn (University of North Carolina), Y Nakamura (University of Tokyo), K Ravichandran (University of Virginia), and M Rasband (Baylor College of Medicine) for providing DNA constructs. We also thank N Heisterkamp (Children’s Hospital Los Angeles) for creating and sharing the Bcr KO mice. We also thank M Taylor, K Firozi, T Munjal, K Um, and B Schwechter for technical assistance. This work was supported by National Institute of Neurological Disorders and Stroke grant R01NS062829 (KFT), National Institute of Mental Health grants R01MH109511 (KFT) and K01MH089112 (JGD), and the Mission Connect-TIRR Foundation (KFT).
Publisher Copyright:
© Duman et al.
PY - 2019/8
Y1 - 2019/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071620246&partnerID=8YFLogxK
U2 - 10.7554/eLife.47566
DO - 10.7554/eLife.47566
M3 - Article
C2 - 31461398
AN - SCOPUS:85071620246
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - e47566
ER -