PT - JOURNAL ARTICLE AU - Torsten Giesemann AU - Günter Schwarz AU - Ralph Nawrotzki AU - Kerstin Berhörster AU - Martin Rothkegel AU - Kathrin Schlüter AU - Nils Schrader AU - Hermann Schindelin AU - Ralf R. Mendel AU - Joachim Kirsch AU - Brigitte M. Jockusch TI - Complex Formation between the Postsynaptic Scaffolding Protein Gephyrin, Profilin, and Mena: A Possible Link to the Microfilament System AID - 10.1523/JNEUROSCI.23-23-08330.2003 DP - 2003 Sep 10 TA - The Journal of Neuroscience PG - 8330--8339 VI - 23 IP - 23 4099 - http://www.jneurosci.org/content/23/23/8330.short 4100 - http://www.jneurosci.org/content/23/23/8330.full SO - J. Neurosci.2003 Sep 10; 23 AB - Gephyrin is an essential component of the postsynaptic cortical protein network of inhibitory synapses. Gephyrin-based scaffolds participate in the assembly as well as the dynamics of receptor clusters by connecting the cytoplasmic domains of glycine and GABAA receptor polypeptides to two cytoskeletal systems, microtubules and microfilaments. Although there is evidence for a physical linkage between gephyrin and microtubules, the interaction between gephyrin and microfilaments is not well understood so far. Here, we show that neuronal gephyrin interacts directly with key regulators of microfilament dynamics, profilin I and neuronal profilin IIa, and with microfilament adaptors of the mammalian enabled (Mena)/vasodilator stimulated phosphoprotein (VASP) family, including neuronal Mena. Profilin and Mena/VASP coprecipitate with gephyrin from tissue and cells, and complex formation requires the E-domain of gephyrin, not the proline-rich central domain. Consequently, gephyrin is not a ligand for the proline-binding motif of profilins, as suspected previously. Instead, it competes with G-actin and phospholipids for the same binding site on profilin. Gephyrin, profilin, and Mena/VASP colocalize at synapses of rat spinal cord and cultivated neurons and in gephyrin clusters expressed in transfected cells. Thus, Mena/VASP and profilin can contribute to the postulated linkage between receptors, gephyrin scaffolds, and the microfilament system and may regulate the microfilament-dependent receptor packing density and dynamics at inhibitory synapses.