Shaping cellular form and function by autophagy.
In addition to its familiar role in non-selective bulk degradation of cellular material, autophagy can also bring about specific changes in the structure and function of cells. Autophagy has been proposed to operate in a substrate-selective mode to carry out this function, although evidence to demonstrate selectivity has been lacking. A recent study of synapse formation in the nervous system of the nematode Caenorhabditis elegans now provides experimental evidence for substrate-selective autophagy. Synapses form when presynaptic cells contact their postsynaptic partners during development. This contact induces the assembly of synaptically-localized protein complexes in the postsynaptic cell that contain scaffolding proteins and neurotransmitter receptors. When presynaptic contact was blocked, autophagy in the postsynaptic cell was induced. Substrate selectivity was evident in this system: the gamma-aminobutyric acid type A receptor (GABA(A) receptor), an integral-membrane neurotransmitter receptor, trafficked from the cell surface to autophagosomes. By contrast, the acetylcholine receptor, a structurally-similar neurotransmitter receptor, remained on the cell surface. This result provides experimental support for the idea that autophagy can bring about changes in cell structure and behavior by degrading specific cellular proteins, particularly cell surface receptors that are often important for regulating cell growth, differentiation and function.
Bamber
Bruce A
BA
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, USA. bamber@hsc.utah.edu
Rowland
Aaron M
AM
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000502:physiology; D002468:Cell Physiological Phenomena; D048430:Cell Shape / Q000502:physiology*; D008954:Models, Biological; D011963:Receptors, GABA-A / Q000502:physiology
D011963:Receptors, GABA-A