A GTPase-induced switch in phospholipid affinity of collybistin contributes to synaptic gephyrin clustering
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A GTPase-induced switch in phospholipid affinity of collybistin contributes to synaptic gephyrin clustering. / Kilisch, Markus; Mayer, Simone; Mitkovski, Miso; Roehse, Heiko; Hentrich, Jennifer; Schwappach, Blanche; Papadopoulos, Theofilos.
in: J CELL SCI, Jahrgang 133, Nr. 2, 23.01.2020.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - A GTPase-induced switch in phospholipid affinity of collybistin contributes to synaptic gephyrin clustering
AU - Kilisch, Markus
AU - Mayer, Simone
AU - Mitkovski, Miso
AU - Roehse, Heiko
AU - Hentrich, Jennifer
AU - Schwappach, Blanche
AU - Papadopoulos, Theofilos
N1 - © 2020. Published by The Company of Biologists Ltd.
PY - 2020/1/23
Y1 - 2020/1/23
N2 - Synaptic transmission between neurons relies on the exact spatial organization of postsynaptic transmitter receptors, which are recruited and positioned by dedicated scaffolding and regulatory proteins. At GABAergic synapses, the regulatory protein collybistin (Cb, also known as ARHGEF9) interacts with small GTPases, cell adhesion proteins and phosphoinositides to recruit the scaffolding protein gephyrin and GABAA receptors to nascent synapses. We dissected the interaction of Cb with the small Rho-like GTPase TC10 (also known as RhoQ) and phospholipids. Our data define a protein-lipid interaction network that controls the clustering of gephyrin at synapses. Within this network, TC10 and monophosphorylated phosphoinositides, particulary phosphatidylinositol 3-phosphate (PI3P), provide a coincidence detection platform that allows the accumulation and activation of Cb in endomembranes. Upon activation, TC10 induces a phospholipid affinity switch in Cb, which allows Cb to specifically interact with phosphoinositide species present at the plasma membrane. We propose that this GTPase-based regulatory switch mechanism represents an important step in the process of tethering of Cb-dependent scaffolds and receptors at nascent postsynapses.
AB - Synaptic transmission between neurons relies on the exact spatial organization of postsynaptic transmitter receptors, which are recruited and positioned by dedicated scaffolding and regulatory proteins. At GABAergic synapses, the regulatory protein collybistin (Cb, also known as ARHGEF9) interacts with small GTPases, cell adhesion proteins and phosphoinositides to recruit the scaffolding protein gephyrin and GABAA receptors to nascent synapses. We dissected the interaction of Cb with the small Rho-like GTPase TC10 (also known as RhoQ) and phospholipids. Our data define a protein-lipid interaction network that controls the clustering of gephyrin at synapses. Within this network, TC10 and monophosphorylated phosphoinositides, particulary phosphatidylinositol 3-phosphate (PI3P), provide a coincidence detection platform that allows the accumulation and activation of Cb in endomembranes. Upon activation, TC10 induces a phospholipid affinity switch in Cb, which allows Cb to specifically interact with phosphoinositide species present at the plasma membrane. We propose that this GTPase-based regulatory switch mechanism represents an important step in the process of tethering of Cb-dependent scaffolds and receptors at nascent postsynapses.
U2 - 10.1242/jcs.232835
DO - 10.1242/jcs.232835
M3 - SCORING: Journal article
C2 - 31932505
VL - 133
JO - J CELL SCI
JF - J CELL SCI
SN - 0021-9533
IS - 2
ER -
