RRC ID 45558
著者 Edwards SL, Yorks RM, Morrison LM, Hoover CM, Miller KG.
タイトル Synapse-Assembly Proteins Maintain Synaptic Vesicle Cluster Stability and Regulate Synaptic Vesicle Transport in Caenorhabditis elegans.
ジャーナル Genetics
Abstract The functional integrity of neurons requires the bidirectional active transport of synaptic vesicles (SVs) in axons. The kinesin motor KIF1A transports SVs from somas to stable SV clusters at synapses, while dynein moves them in the opposite direction. However, it is unclear how SV transport is regulated and how SVs at clusters interact with motor proteins. We addressed these questions by isolating a rare temperature-sensitive allele of Caenorhabditis elegans unc-104 (KIF1A) that allowed us to manipulate SV levels in axons and dendrites. Growth at 20° and 14° resulted in locomotion rates that were ∼3 and 50% of wild type, respectively, with similar effects on axonal SV levels. Corresponding with the loss of SVs from axons, mutants grown at 14° and 20° showed a 10- and 24-fold dynein-dependent accumulation of SVs in their dendrites. Mutants grown at 14° and switched to 25° showed an abrupt irreversible 50% decrease in locomotion and a 50% loss of SVs from the synaptic region 12-hr post-shift, with no further decreases at later time points, suggesting that the remaining clustered SVs are stable and resistant to retrograde removal by dynein. The data further showed that the synapse-assembly proteins SYD-1, SYD-2, and SAD-1 protected SV clusters from degradation by motor proteins. In syd-1, syd-2, and sad-1 mutants, SVs accumulate in an UNC-104-dependent manner in the distal axon region that normally lacks SVs. In addition to their roles in SV cluster stability, all three proteins also regulate SV transport.
巻・号 201(1)
ページ 91-116
公開日 2015-9-1
DOI 10.1534/genetics.115.177337
PII 201/1/91
PMID 26354975
PMC PMC4566279
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism* Dendrites / metabolism Dyneins / metabolism Intercellular Signaling Peptides and Proteins Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Mutation Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / metabolism Phosphoproteins / genetics Phosphoproteins / metabolism* Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Synapses / metabolism Synaptic Transmission Synaptic Vesicles / metabolism* Temperature
IF 4.015
引用数 6
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm6234