Open AccessA GTPase-induced switch in phospholipid affinity of collybistin contributes to synaptic gephyrin clustering
Author(s) -
Markus Kilisch,
Simone Mayer,
Mišo Mitkovski,
Heiko Roehse,
Jennifer Hentrich,
Blanche Schwappach,
Theofilos Papadopoulos
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.232835
Subject(s) - gephyrin , gtpase , biology , microbiology and biotechnology , scaffold protein , gtpase activating protein , neurotransmission , postsynaptic potential , small gtpase , receptor , biochemistry , signal transduction , g protein , glycine receptor , glycine , amino acid
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) 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 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.