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A conformational switch in collybistin determines the differentiation of inhibitory postsynapses.

Soykan T, Schneeberger D, Tria G, Buechner C, Bader N, Svergun D, Tessmer I, Poulopoulos A, Papadopoulos T, Varoqueaux F, Schindelin H, Brose N
EMBO J 33 2113-33 (2014)
Cited: 52 times
EuropePMC logo PMID: 25082542

Abstract

The formation of neuronal synapses and the dynamic regulation of their efficacy depend on the assembly of the postsynaptic neurotransmitter receptor apparatus. Receptor recruitment to inhibitory GABAergic and glycinergic synapses is controlled by the scaffold protein gephyrin and the adaptor protein collybistin. We derived new insights into the structure of collybistin and used these to design biochemical, cell biological, and genetic analyses of collybistin function. Our data define a collybistin-based protein interaction network that controls the gephyrin content of inhibitory postsynapses. Within this network, collybistin can adopt open/active and closed/inactive conformations to act as a switchable adaptor that links gephyrin to plasma membrane phosphoinositides. This function of collybistin is regulated by binding of the adhesion protein neuroligin-2, which stabilizes the open/active conformation of collybistin at the postsynaptic plasma membrane by competing with an intramolecular interaction in collybistin that favors the closed/inactive conformation. By linking trans-synaptic neuroligin-dependent adhesion and phosphoinositide signaling with gephyrin recruitment, the collybistin-based regulatory switch mechanism represents an integrating regulatory node in the formation and function of inhibitory postsynapses.

Articles - 4mt7 mentioned but not cited (4)

  1. A conformational switch in collybistin determines the differentiation of inhibitory postsynapses. Soykan T, Schneeberger D, Tria G, Buechner C, Bader N, Svergun D, Tessmer I, Poulopoulos A, Papadopoulos T, Varoqueaux F, Schindelin H, Brose N. EMBO J 33 2113-2133 (2014)
  2. Targeting GABAAR-Associated Proteins: New Modulators, Labels and Concepts. Khayenko V, Maric HM. Front Mol Neurosci 12 162 (2019)
  3. Mutation p.R356Q in the Collybistin Phosphoinositide Binding Site Is Associated With Mild Intellectual Disability. Chiou TT, Long P, Schumann-Gillett A, Kanamarlapudi V, Haas SA, Harvey K, O'Mara ML, De Blas AL, Kalscheuer VM, Harvey RJ. Front Mol Neurosci 12 60 (2019)
  4. Deciphering the conformational dynamics of gephyrin-mediated collybistin activation. Imam N, Choudhury S, Hemmen K, Heinze KG, Schindelin H. Biophys Rep (N Y) 2 100079 (2022)


Reviews citing this publication (16)

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Articles citing this publication (32)

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