title: CSPGs inhibit axon branching by impairing mitochondria-dependent regulation of actin dynamics and axonal translation.
abstract: Chondroitin sulfate proteoglycans (CSPGs) inhibit the formation of axon collateral branches. The regulation of the axonal cytoskeleton and mitochondria are important components of the mechanism of branching. Actin-dependent axonal plasticity, reflected in the dynamics of axonal actin patches and filopodia, is greatest along segments of the axon populated by mitochondria. It is reported that CSPGs partially depolarize the membrane potential of axonal mitochondria, which impairs the dynamics of the axonal actin cytoskeleton and decreases the formation and duration of axonal filopodia, the first steps in the mechanism of branching. The effects of CSPGs on actin cytoskeletal dynamics are specific to axon segments populated by mitochondria. In contrast, CSPGs do not affect the microtubule content of axons, or the localization of microtubules into axonal filopodia, a required step in the mechanism of branch formation. It is also reported that CSPGs decrease the mitochondria-dependent axonal translation of cortactin, an actin associated protein involved in branching. Finally, the inhibitory effects of CSPGs on axon branching, actin cytoskeletal dynamics and the axonal translation of cortactin are reversed by culturing neurons with acetyl-l-carnitine, which promotes mitochondrial respiration. Collectively these data indicate that CSPGs impair mitochondrial function in axons, an effect which contributes to the inhibition of axon branching. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017.
authors.affiliation: Temple University School of Medicine, Department of Anatomy and Cell Biology, Shriners Hospitals Pediatric Research Center, 3500 N Broad St, Philadelphia, Pennsylvania.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Sainath
authors.affiliation: Temple University School of Medicine, Department of Anatomy and Cell Biology, Shriners Hospitals Pediatric Research Center, 3500 N Broad St, Philadelphia, Pennsylvania.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ketschek
authors.affiliation: Temple University School of Medicine, Department of Anatomy and Cell Biology, Shriners Hospitals Pediatric Research Center, 3500 N Broad St, Philadelphia, Pennsylvania.
authors.forename: Leah
authors.initials: L
authors.lastname: Grandi
authors.affiliation: Temple University School of Medicine, Department of Anatomy and Cell Biology, Shriners Hospitals Pediatric Research Center, 3500 N Broad St, Philadelphia, Pennsylvania.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gallo
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002642:Chick Embryo; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D051356:Cortactin / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism*
chemical_list: D000199:Actins; D011508:Chondroitin Sulfate Proteoglycans; D051356:Cortactin
keywords: acetyl-l-carnitine; actin patch; axon sprouting; cortactin; mitochondria