QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 14, 2004, 24(2):378-388; doi:10.1523/JNEUROSCI.3865-03.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (26) Citing Articles via Google Scholar Google Scholar Articles by Parker, M. J. Articles by Feng, G. Search for Related Content PubMed PubMed Citation Articles by Parker, M. J. Articles by Feng, G.

 Previous Article  |  Next Article 

Cellular/Molecular
PSD93 Regulates Synaptic Stability at Neuronal Cholinergic Synapses

Michael J. Parker,¹ Shengli Zhao,¹ David S. Bredt,³ Joshua R. Sanes,⁴ and Guoping Feng^1,2

Departments of ¹Neurobiology and ²Pathology, Duke University Medical Center, Durham, North Carolina 27710, ³Department of Physiology, University of California at San Francisco, School of Medicine, San Francisco, California 94143, and ⁴Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110

Neuronal cholinergic synapses play important roles in both the PNS and CNS. However, the mechanisms that regulate the formation, maturation, and stability of neuronal cholinergic synapses are poorly understood. In this study, we use the readily accessible mouse superior cervical ganglion (SCG) and submandibular ganglion (SMG) to examine the assembly of the postsynaptic complex of neuronal cholinergic synapses. We find that novel splicing forms of PSD93 (postsynaptic density 93) are expressed in SCG. By immunostaining, we show that PSD93 proteins precisely colocalize with neuronal nicotinic acetylcholine receptors (nAChRs) at synapses of the SCG and SMG. Subcellular fractionation demonstrates that PSD93 is enriched in the PSD fraction of SCG, and coimmunoprecipitation shows that PSD93 and neuronal nAChRs form a complex in vivo. Furthermore, two additional components of the well characterized glutamatergic postsynaptic complex, GKAP/SAPAP (guanylate kinase domain-associated protein/synapse-associated protein-associated protein) and Shank/ProSAP family proteins, are also present at neuronal cholinergic synapses. To assess the function of this protein complex at neuronal cholinergic synapses in vivo, we examined ganglia in mice that lack PSD93. We find that neuronal cholinergic synapses form properly in PSD93 null mice. After denervation, however, synaptic clusters of nAChRs disassemble much faster in mice lacking PSD93 than those in wild-type mice. These results demonstrate that PSD93 is a key component of the postsynaptic scaffold at neuronal cholinergic synapses and plays an important role in synaptic stability. In addition, these results suggest that the mechanism of postsynaptic scaffolding is conserved between neuronal cholinergic and glutamatergic synapses.

Key words: PSD93; PSD95; MAGUKs; cholinergic; nicotinic acetylcholine receptor; synapse; stability; denervation; superior cervical ganglion; submandibular ganglia

---

Received Aug 19, 2003; revised October 7, 2003; accepted October 8, 2003.

This article has been cited by other articles:

				B. A. Johnson, N. Aoyama, N. H. Friedell, S. Ikeda, and A. Ikeda Genetic Modification of the Schisis Phenotype in a Mouse Model of X-Linked Retinoschisis Genetics, March 1, 2008; 178(3): 1785 - 1794. [Abstract] [Full Text] [PDF]

				T. Ravasi, H. Suzuki, K. C. Pang, S. Katayama, M. Furuno, R. Okunishi, S. Fukuda, K. Ru, M. C. Frith, M. M. Gongora, et al. Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome Genome Res., January 1, 2006; 16(1): 11 - 19. [Abstract] [Full Text] [PDF]

				M. B. Ficklin, S. Zhao, and G. Feng Ubiquilin-1 Regulates Nicotine-induced Up-regulation of Neuronal Nicotinic Acetylcholine Receptors J. Biol. Chem., October 7, 2005; 280(40): 34088 - 34095. [Abstract] [Full Text] [PDF]

				Z. Liu, A. W. Tearle, Q. Nai, and D. K. Berg Rapid Activity-Driven SNARE-Dependent Trafficking of Nicotinic Receptors on Somatic Spines J. Neurosci., February 2, 2005; 25(5): 1159 - 1168. [Abstract] [Full Text] [PDF]

				M. L. Leyland and C. Dart An Alternatively Spliced Isoform of PSD-93/Chapsyn 110 Binds to the Inwardly Rectifying Potassium Channel, Kir2.1 J. Biol. Chem., October 15, 2004; 279(42): 43427 - 43436. [Abstract] [Full Text] [PDF]

				M. K. Temburni, M. M. Rosenberg, N. Pathak, R. McConnell, and M. H. Jacob Neuronal Nicotinic Synapse Assembly Requires the Adenomatous Polyposis Coli Tumor Suppressor Protein J. Neurosci., July 28, 2004; 24(30): 6776 - 6784. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help