title: Autophagy negatively regulates early axon growth in cortical neurons.
abstract: Neurite growth requires neurite extension and retraction, which are associated with protein degradation. Autophagy is a conserved bulk degradation pathway that regulates several cellular processes. However, little is known about autophagic regulation during early neurite growth. In this study, we investigated whether autophagy was involved in early neurite growth and how it regulated neurite growth in primary cortical neurons. Components of autophagy were expressed and autophagy was activated during early neurite growth. Interestingly, inhibition of autophagy by atg7 small interfering RNA (siRNA) caused elongation of axons, while activation of autophagy by rapamycin suppressed axon growth. Surprisingly, inhibition of autophagy reduced the protein level of RhoA. Moreover, expression of RhoA suppressed axon overelongation mediated by autophagy inhibition, whereas inhibition of the RhoA signaling pathway by Y-27632 recovered rapamycin-mediated suppression of axon growth. Interestingly, hnRNP-Q1, which negatively regulates RhoA, accumulated in autophagy-deficient neurons, while its protein level was reduced by autophagy activation. Overall, our study suggests that autophagy negatively regulates axon extension via the RhoA-ROCK pathway by regulating hnRNP-Q1 in primary cortical neurons. Therefore, autophagy might serve as a fine-tuning mechanism to regulate early axon extension.
authors.affiliation: Department of Biological Sciences and Biotechnology, College of Life Science and Nanotechnology, Hannam University, Daejeon, South Korea.
authors.forename: Byung-Kwan
authors.initials: BK
authors.lastname: Ban
authors.forename: Mi-Hee
authors.initials: MH
authors.lastname: Jun
authors.forename: Hyun-Hee
authors.initials: HH
authors.lastname: Ryu
authors.forename: Deok-Jin
authors.initials: DJ
authors.lastname: Jang
authors.forename: S Tariq
authors.initials: ST
authors.lastname: Ahmad
authors.forename: Jin-A
authors.initials: JA
authors.lastname: Lee
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D000071193:Autophagy-Related Protein 7; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology; D013997:Time Factors; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000577:Amides; C561242:Atg7 protein, rat; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D011725:Pyridines; C108830:Y 27632; C578418:ROCK1 protein, rat; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes; D020123:Sirolimus
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