DOI: 10.1523/jneurosci.23-23-08330.2003. Complex Formation between the Postsynaptic Scaffolding Protein Gephyrin, Profilin, and Mena: A Possible Link to the Microfilament System

Complex Formation between the Postsynaptic Scaffolding Protein Gephyrin, Profilin, and Mena: A Possible Link to the Microfilament System

10.1523/jneurosci.23-23-08330.2003

Crossref journal-article

Society for Neuroscience

The Journal of Neuroscience (393)

Abstract

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 GABAAreceptor 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.

Bibliography

Giesemann, T., Schwarz, G., Nawrotzki, R., BerhÃ¶rster, K., Rothkegel, M., SchlÃ¼ter, K., Schrader, N., Schindelin, H., Mendel, R. R., Kirsch, J., & Jockusch, B. M. (2003). Complex Formation between the Postsynaptic Scaffolding Protein Gephyrin, Profilin, and Mena: A Possible Link to the Microfilament System. The Journal of Neuroscience, 23(23), 8330â8339.

Authors 11

Torsten Giesemann (first)
Günter Schwarz (additional)
Ralph Nawrotzki (additional)
Kerstin Berhörster (additional)
Martin Rothkegel (additional)
Kathrin Schlüter (additional)
Nils Schrader (additional)
Hermann Schindelin (additional)
Ralf R. Mendel (additional)
Joachim Kirsch (additional)
Brigitte M. Jockusch (additional)

References 42 Referenced 101

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10.1016/S0960-9822(02)00912-0
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Dates

Type	When
Created	7 years, 4 months ago (April 10, 2018, 5:16 p.m.)
Deposited	2 years, 6 months ago (Feb. 23, 2023, 11:13 a.m.)
Indexed	2 days, 22 hours ago (Sept. 4, 2025, 10:11 a.m.)
Issued	21 years, 11 months ago (Sept. 10, 2003)
Published	21 years, 11 months ago (Sept. 10, 2003)
Published Online	21 years, 11 months ago (Sept. 10, 2003)
Published Print	21 years, 11 months ago (Sept. 10, 2003)

Funders 0

None

BibTeX

@article{Giesemann_2003, title={Complex Formation between the Postsynaptic Scaffolding Protein Gephyrin, Profilin, and Mena: A Possible Link to the Microfilament System}, volume={23}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.23-23-08330.2003}, DOI={10.1523/jneurosci.23-23-08330.2003}, number={23}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Giesemann, Torsten and Schwarz, Günter and Nawrotzki, Ralph and Berhörster, Kerstin and Rothkegel, Martin and Schlüter, Kathrin and Schrader, Nils and Schindelin, Hermann and Mendel, Ralf R. and Kirsch, Joachim and Jockusch, Brigitte M.}, year={2003}, month=sep, pages={8330–8339} }

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