RRC ID 4314
著者 Wang W, Bouhours M, Gracheva EO, Liao EH, Xu K, Sengar AS, Xin X, Roder J, Boone C, Richmond JE, Zhen M, Egan SE.
タイトル ITSN-1 controls vesicle recycling at the neuromuscular junction and functions in parallel with DAB-1.
ジャーナル Traffic
Abstract Intersectins (Itsn) are conserved EH and SH3 domain containing adaptor proteins. In Drosophila melanogaster, ITSN is required to regulate synaptic morphology, to facilitate efficient synaptic vesicle recycling and for viability. Here, we report our genetic analysis of Caenorhabditis elegans intersectin. In contrast to Drosophila, C. elegans itsn-1 protein null mutants are viable and display grossly normal locomotion and development. However, motor neurons in these mutants show a dramatic increase in large irregular vesicles and accumulate membrane-associated vesicles at putative endocytic hotspots, approximately 300 nm from the presynaptic density. This defect occurs precisely where endogenous ITSN-1 protein localizes in wild-type animals and is associated with a significant reduction in synaptic vesicle number and reduced frequency of endogenous synaptic events at neuromuscular junctions (NMJs). ITSN-1 forms a stable complex with EHS-1 (Eps15) and is expressed at reduced levels in ehs-1 mutants. Thus, ITSN-1 together with EHS-1, coordinate vesicle recycling at C. elegans NMJs. We also found that both itsn-1 and ehs-1 mutants show poor viability and growth in a Disabled (dab-1) null mutant background. These results show for the first time that intersectin and Eps15 proteins function in the same genetic pathway, and appear to function synergistically with the clathrin-coat-associated sorting protein, Disabled, for viability.
巻・号 9(5)
ページ 742-54
公開日 2008-5-1
DOI 10.1111/j.1600-0854.2008.00712.x
PII TRA712
PMID 18298590
PMC PMC3791081
MeSH Adaptor Proteins, Vesicular Transport / genetics Adaptor Proteins, Vesicular Transport / metabolism* Animals Animals, Genetically Modified Caenorhabditis elegans / anatomy & histology Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Drosophila melanogaster Endocytosis Gene Deletion Genes, Reporter Humans Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism Neuromuscular Junction / physiology* Patch-Clamp Techniques Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Synapses / metabolism Synapses / ultrastructure Synaptic Transmission / physiology Synaptic Vesicles / metabolism* Synaptic Vesicles / ultrastructure Two-Hybrid System Techniques
IF 4.045
引用数 25
WOS 分野 CELL BIOLOGY
リソース情報
線虫 tm725 tm2156 tm268