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The Journal of Neuroscience, February 8, 2006, 26(6):1711-1720; doi:10.1523/JNEUROSCI.2279-05.2006

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Cellular/Molecular
Presynaptic Terminals Independently Regulate Synaptic Clustering and Autophagy of GABA_A Receptors in Caenorhabditis elegans

Aaron M. Rowland,¹ Janet E. Richmond,² Jason G. Olsen,¹ David H. Hall,³ and Bruce A. Bamber¹

¹Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, ²Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, and ³Center for Caenorhabditis elegans Anatomy, Albert Einstein College of Medicine, Bronx, New York 10461

Correspondence should be addressed to Bruce A. Bamber, Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East, Room 201, Salt Lake City, UT 84112. Email: bamber{at}hsc.utah.edu

Synaptic clustering of GABA_A receptors is important for the function of inhibitory synapses, influencing synapse strength and, consequently, the balance of excitation and inhibition in the brain. Presynaptic terminals are known to induce GABA_A receptor clustering during synaptogenesis, but the mechanisms of cluster formation and maintenance are not known. To study how presynaptic neurons direct the formation of GABA_A receptor clusters, we have investigated GABA_A receptor localization in postsynaptic cells that fail to receive presynaptic contacts in Caenorhabditis elegans. Postsynaptic muscles in C. elegans receive acetylcholine and GABA motor innervation, and GABA_A receptors cluster opposite GABA terminals. Selective loss of GABA inputs caused GABA_A receptors to be diffusely distributed at or near the muscle cell surface, confirming that GABA presynaptic terminals induce GABA_A receptor clustering. In contrast, selective loss of acetylcholine innervation had no effect on GABA_A receptor localization. However, loss of both GABA and acetylcholine inputs together caused GABA_A receptors to traffic to intracellular autophagosomes. Autophagosomes normally transport bulk cytoplasm to the lysosome for degradation. However, we show that GABA_A receptors traffic to autophagosomes after endocytic removal from the cell surface and that acetylcholine receptors in the same cells do not traffic to autophagosomes. Thus, autophagy can degrade cell-surface receptors and can do so selectively. Our results show that presynaptic terminals induce GABA_A receptor clustering by independently controlling synaptic localization and surface stability of GABA_A receptors. They also demonstrate a novel function for autophagy in GABA_A receptor degradative trafficking.

Key words: GABA_A receptor; autophagy; synaptogenesis; UNC-49; nicotinic acetylcholine receptor; C. elegans

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Received Dec. 1, 2004; revised Nov. 29, 2005; accepted Dec. 28, 2005.

Correspondence should be addressed to Bruce A. Bamber, Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East, Room 201, Salt Lake City, UT 84112. Email: bamber{at}hsc.utah.edu

This article has been cited by other articles:

				S. M. Garcia, M. O. Casanueva, M. C. Silva, M. D. Amaral, and R. I. Morimoto Neuronal signaling modulates protein homeostasis in Caenorhabditis elegans post-synaptic muscle cells Genes & Dev., November 15, 2007; 21(22): 3006 - 3016. [Abstract] [Full Text] [PDF]

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