@article{69aa1b93c5634f8692f9081c5b79899f,
title = "KIF1A/UNC-104 Transports ATG-9 to Regulate Neurodevelopment and Autophagy at Synapses",
abstract = "Autophagy is a cellular degradation process important for neuronal development and survival. Neurons are highly polarized cells in which autophagosome biogenesis is spatially compartmentalized. The mechanisms and physiological importance of this spatial compartmentalization of autophagy in the neuronal development of living animals are not well understood. Here we determine that, in Caenorhabditis elegans neurons, autophagosomes form near synapses and are required for neurodevelopment. We first determine, through unbiased genetic screens and systematic genetic analyses, that autophagy is required cell autonomously for presynaptic assembly and for axon outgrowth dynamics in specific neurons. We observe autophagosome biogenesis in the axon near synapses, and this localization depends on the synaptic vesicle kinesin, KIF1A/UNC-104. KIF1A/UNC-104 coordinates localized autophagosome formation by regulating the transport of the integral membrane autophagy protein, ATG-9. Our findings indicate that autophagy is spatially regulated in neurons through the transport of ATG-9 by KIF1A/UNC-104 to regulate neurodevelopment.",
author = "Stavoe, {Andrea K.H.} and Hill, {Sarah E.} and Hall, {David H.} and Col{\'o}n-Ramos, {Daniel A.}",
note = "Funding Information: We thank members of the Col{\'o}n-Ramos lab, Erika Holzbaur (University of Pennsylvania), Hannes Buelow (Albert Einstein College of Medicine), and Alicia Mel{\'e}ndez (Queens College, CUNY) for their thoughtful comments on the manuscript and the project. We are particularly indebted to Kang Shen (Stanford University) for reagents, thoughtful comments, and advice during the course of this project. We thank summer interns Jihane Jadi (University of North Carolina, Chapel Hill) and Ninoshka Caballero-Col{\'o}n (University of Puerto Rico, Humacao) for experimental assistance. We thank the Caenorhabditis Genetics Center for mutant strains, Cori Bargmann (Rockefeller University) for CX9797 (kyIs445) strain, David Miller (Vanderbilt University) for NC1686 (wdIs51) strain, the Mitani laboratory of the Tokyo Women's Medical University School of Medicine for autophagy mutant strains, and the Hong Zhang laboratory at the Institute of Biophysics, Chinese Academy of Sciences for autophagy mutant alleles. We thank Z. Altun (www.wormatlas.org) for diagrams used in the figures. We thank Bob Goldstein (University of North Carolina at Chapel Hill) for CRISPR self-excision cassette (SEC) constructs and advice. We are grateful to Steven Cook for his help in choosing and copying high-resolution electron micrographs from the Hall lab archive. We thank John White and Jonathan Hodgkin for their help in contributing thousands of electron micrographs from the MRC/LMB collection to the Hall lab. We thank the Research Center for Minority Institutions program and the Instituto de Neurobiolog{\'i}a de la Universidad de Puerto Rico for providing a meeting and brainstorming platform. This work was partially conducted at the Marine Biological Laboratories at Woods Hole, under a Whitman research award to D.A.C.R. This work was funded by NIH grants to D.A.C.R. (U01HD075602, R01NS076558, and R24OD016474). D.H.H., the Center of C. elegans Anatomy, and www.wormimage.org were supported by NIH OD 010943. A.K.H.S. and S.E.H. were supported by Cellular and Molecular Biology Training grant T32-GM007223 from the NIH. S.E.H. was also supported by NSF Graduate Research Fellowship DGE-1122492. Funding Information: We thank members of the Col{\'o}n-Ramos lab, Erika Holzbaur (University of Pennsylvania), Hannes Buelow (Albert Einstein College of Medicine), and Alicia Mel{\'e}ndez (Queens College, CUNY) for their thoughtful comments on the manuscript and the project. We are particularly indebted to Kang Shen (Stanford University) for reagents, thoughtful comments, and advice during the course of this project. We thank summer interns Jihane Jadi (University of North Carolina, Chapel Hill) and Ninoshka Caballero-Col{\'o}n (University of Puerto Rico, Humacao) for experimental assistance. We thank the Caenorhabditis Genetics Center for mutant strains, Cori Bargmann (Rockefeller University) for CX9797 ( kyIs445 ) strain, David Miller (Vanderbilt University) for NC1686 ( wdIs51 ) strain, the Mitani laboratory of the Tokyo Women's Medical University School of Medicine for autophagy mutant strains, and the Hong Zhang laboratory at the Institute of Biophysics, Chinese Academy of Sciences for autophagy mutant alleles. We thank Z. Altun ( www.wormatlas.org ) for diagrams used in the figures. We thank Bob Goldstein (University of North Carolina at Chapel Hill) for CRISPR self-excision cassette (SEC) constructs and advice. We are grateful to Steven Cook for his help in choosing and copying high-resolution electron micrographs from the Hall lab archive. We thank John White and Jonathan Hodgkin for their help in contributing thousands of electron micrographs from the MRC/LMB collection to the Hall lab. We thank the Research Center for Minority Institutions program and the Instituto de Neurobiolog{\'i}a de la Universidad de Puerto Rico for providing a meeting and brainstorming platform. This work was partially conducted at the Marine Biological Laboratories at Woods Hole, under a Whitman research award to D.A.C.R. This work was funded by NIH grants to D.A.C.R. ( U01HD075602 , R01NS076558 , and R24OD016474 ). D.H.H., the Center of C. elegans Anatomy, and www.wormimage.org were supported by NIH OD 010943 . A.K.H.S. and S.E.H. were supported by Cellular and Molecular Biology Training grant T32-GM007223 from the NIH. S.E.H. was also supported by NSF Graduate Research Fellowship DGE-1122492 . Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = jul,
day = "25",
doi = "10.1016/j.devcel.2016.06.012",
language = "English (US)",
volume = "38",
pages = "171--185",
journal = "Developmental cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "2",
}