TY - JOUR
T1 - Dynamic Control of Excitatory Synapse Development by a Rac1 GEF/GAP Regulatory Complex
AU - Um, Kyongmi
AU - Niu, Sanyong
AU - Duman, Joseph G.
AU - Cheng, Jinxuan X.
AU - Tu, Yen Kuei
AU - Schwechter, Brandon
AU - Liu, Feng
AU - Hiles, Laura
AU - Narayanan, Anjana S.
AU - Ash, Ryan T.
AU - Mulherkar, Shalaka
AU - Alpadi, Kannan
AU - Smirnakis, Stelios M.
AU - Tolias, Kimberley F.
PY - 2014/6/23
Y1 - 2014/6/23
N2 - The small GTPase Rac1 orchestrates actin-dependent remodeling essential for numerous cellular processes including synapse development. While precise spatiotemporal regulation of Rac1 is necessary for its function, little is known about the mechanisms that enable Rac1 activators (GEFs) and inhibitors (GAPs) to act in concert to regulate Rac1 signaling. Here, we identify a regulatory complex composed of a Rac-GEF (Tiam1) and a Rac-GAP (Bcr) that cooperate to control excitatory synapse development. Disruption of Bcr function within this complex increases Rac1 activity and dendritic spine remodeling, resulting in excessive synaptic growth that is rescued by Tiam1 inhibition. Notably, EphB receptors utilize the Tiam1-Bcr complex to control synaptogenesis. Following EphB activation, Tiam1 induces Rac1-dependent spine formation, whereas Bcr prevents Rac1-mediated receptor internalization, promoting spine growth over retraction. The finding that a Rac-specific GEF/GAP complex is required to maintain optimal levels of Rac1 signaling provides an important insight into the regulation of small GTPases.
AB - The small GTPase Rac1 orchestrates actin-dependent remodeling essential for numerous cellular processes including synapse development. While precise spatiotemporal regulation of Rac1 is necessary for its function, little is known about the mechanisms that enable Rac1 activators (GEFs) and inhibitors (GAPs) to act in concert to regulate Rac1 signaling. Here, we identify a regulatory complex composed of a Rac-GEF (Tiam1) and a Rac-GAP (Bcr) that cooperate to control excitatory synapse development. Disruption of Bcr function within this complex increases Rac1 activity and dendritic spine remodeling, resulting in excessive synaptic growth that is rescued by Tiam1 inhibition. Notably, EphB receptors utilize the Tiam1-Bcr complex to control synaptogenesis. Following EphB activation, Tiam1 induces Rac1-dependent spine formation, whereas Bcr prevents Rac1-mediated receptor internalization, promoting spine growth over retraction. The finding that a Rac-specific GEF/GAP complex is required to maintain optimal levels of Rac1 signaling provides an important insight into the regulation of small GTPases.
UR - https://www.scopus.com/pages/publications/84904704517
U2 - 10.1016/j.devcel.2014.05.011
DO - 10.1016/j.devcel.2014.05.011
M3 - Article
C2 - 24960694
AN - SCOPUS:84904704517
SN - 1534-5807
VL - 29
SP - 701
EP - 715
JO - Developmental cell
JF - Developmental cell
IS - 6
ER -