KIF1A/UNC-104 Transports ATG-9 to Regulate Neurodevelopment and Autophagy at Synapses

Andrea K H Stavoe, Sarah E. Hill, David H. Hall, Daniel A. Colón-Ramos

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)171-185
Number of pages15
JournalDevelopmental Cell
Volume38
Issue number2
DOIs
StatePublished - Jul 25 2016

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Autophagy
Synapses
Neurons
Kinesin
Synaptic Vesicles
Caenorhabditis elegans
Animals
Axons
Membranes
Membrane Proteins
Degradation
Autophagosomes
Proteins

ASJC Scopus subject areas

  • Developmental Biology

Cite this

KIF1A/UNC-104 Transports ATG-9 to Regulate Neurodevelopment and Autophagy at Synapses. / Stavoe, Andrea K H; Hill, Sarah E.; Hall, David H.; Colón-Ramos, Daniel A.

In: Developmental Cell, Vol. 38, No. 2, 25.07.2016, p. 171-185.

Research output: Contribution to journalArticle

Stavoe, Andrea K H ; Hill, Sarah E. ; Hall, David H. ; Colón-Ramos, Daniel A. / KIF1A/UNC-104 Transports ATG-9 to Regulate Neurodevelopment and Autophagy at Synapses. In: Developmental Cell. 2016 ; Vol. 38, No. 2. pp. 171-185.
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